3q96 - Revision history

OCA at 10:46, 21 February 2024

OCA — Wed, 21 Feb 2024 10:46:33 GMT

←Older revision		Revision as of 10:46, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3q96' size='340' side='right'caption='[[3q96]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='3q96' size='340' side='right'caption='[[3q96]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3q96]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q96 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3q96]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q96 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NF:(2S)-N-[3-(2-AMINOPROPAN-2-YL)-5-(TRIFLUOROMETHYL)PHENYL]-7-[(7-OXO-5,6,7,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-4-YL)OXY]-1,2,3,4-TETRAHYDRONAPHTHALENE-2-CARBOXAMIDE'>0NF</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.1Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRAF, BRAF1, RAFB1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NF:(2S)-N-[3-(2-AMINOPROPAN-2-YL)-5-(TRIFLUOROMETHYL)PHENYL]-7-[(7-OXO-5,6,7,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-4-YL)OXY]-1,2,3,4-TETRAHYDRONAPHTHALENE-2-CARBOXAMIDE'>0NF</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3q96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q96 OCA], [https://pdbe.org/3q96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q96 RCSB], [https://www.ebi.ac.uk/pdbsum/3q96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q96 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3q96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q96 OCA], [https://pdbe.org/3q96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q96 RCSB], [https://www.ebi.ac.uk/pdbsum/3q96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q96 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Note=Defects in BRAF are found in a wide range of cancers.<ref>PMID:18974108</ref> Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500]].<ref>PMID:18974108</ref> Defects in BRAF are involved in lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.<ref>PMID:18974108</ref> <ref>PMID:12460919</ref> Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:[https://omim.org/entry/605027 605027]]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.<ref>PMID:18974108</ref> <ref>PMID:14612909</ref> Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[https://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.<ref>PMID:18974108</ref> Defects in BRAF are the cause of Noonan syndrome type 7 (NS7) [MIM:[https://omim.org/entry/613706 613706]]. Noonan syndrome is a disorder characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Defects in BRAF are the cause of LEOPARD syndrome type 3 (LEOPARD3) [MIM:[https://omim.org/entry/613707 613707]]. LEOPARD3 is a disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Note=A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation.<ref>PMID:18974108</ref>	+	[https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN] Note=Defects in BRAF are found in a wide range of cancers.<ref>PMID:18974108</ref> Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500].<ref>PMID:18974108</ref> Defects in BRAF are involved in lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.<ref>PMID:18974108</ref> <ref>PMID:12460919</ref> Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:[https://omim.org/entry/605027 605027]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.<ref>PMID:18974108</ref> <ref>PMID:14612909</ref> Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[https://omim.org/entry/115150 115150]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.<ref>PMID:18974108</ref> Defects in BRAF are the cause of Noonan syndrome type 7 (NS7) [MIM:[https://omim.org/entry/613706 613706]. Noonan syndrome is a disorder characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Defects in BRAF are the cause of LEOPARD syndrome type 3 (LEOPARD3) [MIM:[https://omim.org/entry/613707 613707]. LEOPARD3 is a disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Note=A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation.<ref>PMID:18974108</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.	+	[https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.	+
-		+
-	Design and optimization of potent and orally bioavailable tetrahydronaphthalene raf inhibitors.,Gould AE, Adams R, Adhikari S, Aertgeerts K, Afroze R, Blackburn C, Calderwood EF, Chau R, Chouitar J, Duffey MO, England DB, Farrer C, Forsyth N, Garcia K, Gaulin J, Greenspan PD, Guo R, Harrison SJ, Huang SC, Iartchouk N, Janowick D, Kim MS, Kulkarni B, Langston SP, Liu JX, Ma LT, Menon S, Mizutani H, Paske E, Renou CC, Rezaei M, Rowland RS, Sintchak MD, Smith MD, Stroud SG, Tregay M, Tian Y, Veiby OP, Vos TJ, Vyskocil S, Williams J, Xu T, Yang JJ, Yano J, Zeng H, Zhang DM, Zhang Q, Galvin KM J Med Chem. 2011 Mar 24;54(6):1836-46. Epub 2011 Feb 22. PMID:21341678<ref>PMID:21341678</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3q96" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
Line 29:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Aertgeerts K]]
-	[[Category: Aertgeerts, K]]	+	[[Category: Sintchak MD]]
-	[[Category: Sintchak~~, M D~~]]	+	[[Category: Yano J]]
-	[[Category: Yano, J]]	+
-	~~[[Category: Design]]~~	+
-	~~[[Category: Optimization]]~~	+
-	~~[[Category: Orally bioavailable]]~~	+
-	~~[[Category: Potent]]~~	+
-	~~[[Category: Tetrahydronaphthalene]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 05:58, 8 June 2022

OCA — Wed, 08 Jun 2022 05:58:26 GMT

←Older revision		Revision as of 05:58, 8 June 2022
Line 1:		Line 1:

	==B-Raf kinase domain in complex with a tetrahydronaphthalene inhibitor==		==B-Raf kinase domain in complex with a tetrahydronaphthalene inhibitor==
-	<StructureSection load='3q96' size='340' side='right' caption='[[3q96]], [[Resolution\|resolution]] 3.10Å' scene=''>	+	<StructureSection load='3q96' size='340' side='right'caption='[[3q96]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3q96]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q96 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3Q96 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3q96]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q96 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NF:(2S)-N-[3-(2-AMINOPROPAN-2-YL)-5-(TRIFLUOROMETHYL)PHENYL]-7-[(7-OXO-5,6,7,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-4-YL)OXY]-1,2,3,4-TETRAHYDRONAPHTHALENE-2-CARBOXAMIDE'>0NF</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NF:(2S)-N-[3-(2-AMINOPROPAN-2-YL)-5-(TRIFLUOROMETHYL)PHENYL]-7-[(7-OXO-5,6,7,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-4-YL)OXY]-1,2,3,4-TETRAHYDRONAPHTHALENE-2-CARBOXAMIDE'>0NF</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRAF, BRAF1, RAFB1 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRAF, BRAF1, RAFB1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3q96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q96 OCA], [~~http~~://pdbe.org/3q96 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3q96 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3q96 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3q96 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3q96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q96 OCA], [https://pdbe.org/3q96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q96 RCSB], [https://www.ebi.ac.uk/pdbsum/3q96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q96 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Note=Defects in BRAF are found in a wide range of cancers.<ref>PMID:18974108</ref> Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:[~~http~~://omim.org/entry/114500 114500]].<ref>PMID:18974108</ref> Defects in BRAF are involved in lung cancer (LNCR) [MIM:[~~http~~://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.<ref>PMID:18974108</ref> <ref>PMID:12460919</ref> Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:[~~http~~://omim.org/entry/605027 605027]]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.<ref>PMID:18974108</ref> <ref>PMID:14612909</ref> Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[~~http~~://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.<ref>PMID:18974108</ref> Defects in BRAF are the cause of Noonan syndrome type 7 (NS7) [MIM:[~~http~~://omim.org/entry/613706 613706]]. Noonan syndrome is a disorder characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Defects in BRAF are the cause of LEOPARD syndrome type 3 (LEOPARD3) [MIM:[~~http~~://omim.org/entry/613707 613707]]. LEOPARD3 is a disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Note=A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation.<ref>PMID:18974108</ref>	+	[[https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Note=Defects in BRAF are found in a wide range of cancers.<ref>PMID:18974108</ref> Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500]].<ref>PMID:18974108</ref> Defects in BRAF are involved in lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.<ref>PMID:18974108</ref> <ref>PMID:12460919</ref> Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:[https://omim.org/entry/605027 605027]]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.<ref>PMID:18974108</ref> <ref>PMID:14612909</ref> Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[https://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.<ref>PMID:18974108</ref> Defects in BRAF are the cause of Noonan syndrome type 7 (NS7) [MIM:[https://omim.org/entry/613706 613706]]. Noonan syndrome is a disorder characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Defects in BRAF are the cause of LEOPARD syndrome type 3 (LEOPARD3) [MIM:[https://omim.org/entry/613707 613707]]. LEOPARD3 is a disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Note=A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation.<ref>PMID:18974108</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.	+	[[https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 3q96" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3q96" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Aertgeerts, K]]		[[Category: Aertgeerts, K]]

OCA at 09:12, 8 November 2017

OCA — Wed, 08 Nov 2017 09:12:23 GMT

←Older revision		Revision as of 09:12, 8 November 2017
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 3q96" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3q96" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:42, 5 August 2016

OCA — Fri, 05 Aug 2016 15:42:30 GMT

←Older revision		Revision as of 15:42, 5 August 2016
Line 1:		Line 1:
		+
	==B-Raf kinase domain in complex with a tetrahydronaphthalene inhibitor==		==B-Raf kinase domain in complex with a tetrahydronaphthalene inhibitor==
	<StructureSection load='3q96' size='340' side='right' caption='[[3q96]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='3q96' size='340' side='right' caption='[[3q96]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3q96]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q96 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3q96]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q96 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NF:(2S)-N-[3-(2-AMINOPROPAN-2-YL)-5-(TRIFLUOROMETHYL)PHENYL]-7-[(7-OXO-5,6,7,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-4-YL)OXY]-1,2,3,4-TETRAHYDRONAPHTHALENE-2-CARBOXAMIDE'>0NF</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NF:(2S)-N-[3-(2-AMINOPROPAN-2-YL)-5-(TRIFLUOROMETHYL)PHENYL]-7-[(7-OXO-5,6,7,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-4-YL)OXY]-1,2,3,4-TETRAHYDRONAPHTHALENE-2-CARBOXAMIDE'>0NF</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRAF, BRAF1, RAFB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRAF, BRAF1, RAFB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3q96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q96 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q96 RCSB], [http://www.ebi.ac.uk/pdbsum/3q96 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3q96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q96 OCA], [http://pdbe.org/3q96 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3q96 RCSB], [http://www.ebi.ac.uk/pdbsum/3q96 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3q96 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3q96" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Aertgeerts, K]]		[[Category: Aertgeerts, K]]

OCA at 10:10, 19 December 2014

OCA — Fri, 19 Dec 2014 10:10:58 GMT

←Older revision		Revision as of 10:10, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3q96~~\| ~~PDB~~=3q96 \| ~~SCENE~~= }}	+	==B-Raf kinase domain in complex with a tetrahydronaphthalene inhibitor==
-	===B-~~Raf~~ kinase ~~domain~~ in ~~complex~~ with a ~~tetrahydronaphthalene inhibitor~~===	+	<StructureSection load='3q96' size='340' side='right' caption='[[3q96]], [[Resolution\|resolution]] 3.10Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21341678}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3q96]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q96 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NF:(2S)-N-[3-(2-AMINOPROPAN-2-YL)-5-(TRIFLUOROMETHYL)PHENYL]-7-[(7-OXO-5,6,7,8-TETRAHYDRO-1,8-NAPHTHYRIDIN-4-YL)OXY]-1,2,3,4-TETRAHYDRONAPHTHALENE-2-CARBOXAMIDE'>0NF</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRAF, BRAF1, RAFB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3q96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q96 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q96 RCSB], [http://www.ebi.ac.uk/pdbsum/3q96 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Note=Defects in BRAF are found in a wide range of cancers.<ref>PMID:18974108</ref> Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]].<ref>PMID:18974108</ref> Defects in BRAF are involved in lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.<ref>PMID:18974108</ref> <ref>PMID:12460919</ref> Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:[http://omim.org/entry/605027 605027]]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.<ref>PMID:18974108</ref> <ref>PMID:14612909</ref> Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[http://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.<ref>PMID:18974108</ref> Defects in BRAF are the cause of Noonan syndrome type 7 (NS7) [MIM:[http://omim.org/entry/613706 613706]]. Noonan syndrome is a disorder characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Defects in BRAF are the cause of LEOPARD syndrome type 3 (LEOPARD3) [MIM:[http://omim.org/entry/613707 613707]]. LEOPARD3 is a disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.<ref>PMID:18974108</ref> <ref>PMID:19206169</ref> Note=A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation.<ref>PMID:18974108</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.

-	~~==Disease==~~	+	Design and optimization of potent and orally bioavailable tetrahydronaphthalene raf inhibitors.,Gould AE, Adams R, Adhikari S, Aertgeerts K, Afroze R, Blackburn C, Calderwood EF, Chau R, Chouitar J, Duffey MO, England DB, Farrer C, Forsyth N, Garcia K, Gaulin J, Greenspan PD, Guo R, Harrison SJ, Huang SC, Iartchouk N, Janowick D, Kim MS, Kulkarni B, Langston SP, Liu JX, Ma LT, Menon S, Mizutani H, Paske E, Renou CC, Rezaei M, Rowland RS, Sintchak MD, Smith MD, Stroud SG, Tregay M, Tian Y, Veiby OP, Vos TJ, Vyskocil S, Williams J, Xu T, Yang JJ, Yano J, Zeng H, Zhang DM, Zhang Q, Galvin KM J Med Chem. 2011 Mar 24;54(6):1836-46. Epub 2011 Feb 22. PMID:21341678<ref>PMID:21341678</ref>
-	~~[[http://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Note=Defects in BRAF are found in a wide range~~ of ~~cancers~~.<ref>PMID:18974108</ref> Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]].<ref>PMID:18974108</ref> Defects in BRAF are involved in lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, ~~adenocarcinoma~~, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.<ref>PMID:18974108</ref><ref>PMID:12460919</ref> Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:[http://omim.org/entry/605027 605027]]. NHL is a cancer that starts in cells of the lymph system, ~~which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes~~, fever and weight loss.<ref>PMID:18974108</ref><ref>PMID:14612909</ref> Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[http://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, ~~heart defects and mental retardation. Heart defects include pulmonic stenosis~~, ~~atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse~~, ~~friable hair~~, ~~hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction~~, ~~hypoplastic supraorbital ridges~~, ~~downslanting palpebral fissures~~, ~~a depressed nasal bridge~~, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.<ref>PMID:18974108</ref> Defects in BRAF are the cause of Noonan syndrome type 7 (NS7) [MIM:[http://omim.org/entry/613706 613706]]. Noonan syndrome is a disorder characterized by facial dysmorphic features such as hypertelorism, ~~a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature~~, ~~a short neck with webbing or redundancy of skin~~, ~~cardiac anomalies~~, ~~deafness~~, motor delay and variable intellectual deficits.<ref>PMID:18974108</ref><ref>PMID:19206169</ref> Defects in BRAF are the cause of LEOPARD syndrome type 3 (LEOPARD3) [MIM:[http://omim.org/entry/613707 613707]]. LEOPARD3 is a disorder characterized by lentigines, ~~electrocardiographic conduction abnormalities~~, ~~ocular hypertelorism~~, ~~pulmonic stenosis~~, ~~abnormalities of genitalia~~, ~~retardation of growth~~, ~~and sensorineural deafness~~.~~<ref>PMID~~:~~18974108</ref><ref>~~PMID:19206169</ref> Note=A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation.<ref>PMID:~~18974108~~</ref>	+
-		+
-	~~==Function==~~	+
-	[[http://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3q96]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3Q96 OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:021341678</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Aertgeerts, K.]]	+	[[Category: Aertgeerts, K]]
-	[[Category: Sintchak, M D.]]	+	[[Category: Sintchak, M D]]
-	[[Category: Yano, J.]]	+	[[Category: Yano, J]]
	[[Category: Design]]		[[Category: Design]]
	[[Category: Optimization]]		[[Category: Optimization]]

OCA at 00:59, 25 March 2013

OCA — Mon, 25 Mar 2013 00:59:55 GMT

←Older revision		Revision as of 00:59, 25 March 2013
Line 1:		Line 1:
-	[[Image:3q96.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3q96", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3q96\| PDB=3q96 \| SCENE= }}		{{STRUCTURE_3q96\| PDB=3q96 \| SCENE= }}
-
	===B-Raf kinase domain in complex with a tetrahydronaphthalene inhibitor===		===B-Raf kinase domain in complex with a tetrahydronaphthalene inhibitor===
		+	{{ABSTRACT_PUBMED_21341678}}

		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Note=Defects in BRAF are found in a wide range of cancers.<ref>PMID:18974108</ref> Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]].<ref>PMID:18974108</ref> Defects in BRAF are involved in lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.<ref>PMID:18974108</ref><ref>PMID:12460919</ref> Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:[http://omim.org/entry/605027 605027]]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.<ref>PMID:18974108</ref><ref>PMID:14612909</ref> Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[http://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.<ref>PMID:18974108</ref> Defects in BRAF are the cause of Noonan syndrome type 7 (NS7) [MIM:[http://omim.org/entry/613706 613706]]. Noonan syndrome is a disorder characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits.<ref>PMID:18974108</ref><ref>PMID:19206169</ref> Defects in BRAF are the cause of LEOPARD syndrome type 3 (LEOPARD3) [MIM:[http://omim.org/entry/613707 613707]]. LEOPARD3 is a disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.<ref>PMID:18974108</ref><ref>PMID:19206169</ref> Note=A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation.<ref>PMID:18974108</ref>

-	~~<!--~~	+	==Function==
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21341678}}, adds the Publication Abstract to the page~~	+	[[http://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN]] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron.
-	~~(as it appears on PubMed at~~ http://www.~~pubmed~~.~~gov), where 21341678 is~~ the ~~PubMed ID number~~.	+
-	~~-->~~	+
-	~~{{ABSTRACT_PUBMED_21341678}}~~	+

	==About this Structure==		==About this Structure==
Line 22:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021341678</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021341678</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
Line 28:		Line 19:
	[[Category: Sintchak, M D.]]		[[Category: Sintchak, M D.]]
	[[Category: Yano, J.]]		[[Category: Yano, J.]]
		+	[[Category: Design]]
		+	[[Category: Optimization]]
		+	[[Category: Orally bioavailable]]
		+	[[Category: Potent]]
		+	[[Category: Tetrahydronaphthalene]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:10, 4 May 2011

OCA — Wed, 04 May 2011 06:10:36 GMT

←Older revision		Revision as of 06:10, 4 May 2011
Line 1:		Line 1:
-	[[Image:3q96.~~jpg~~\|left\|200px]]	+	[[Image:3q96.png\|left\|200px]]

	<!--		<!--
Line 22:		Line 22:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~21341678~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021341678</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]

OCA at 07:04, 23 March 2011

OCA — Wed, 23 Mar 2011 07:04:34 GMT

←Older revision		Revision as of 07:04, 23 March 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3q96.jpg\|left\|200px]]

-	The ~~entry 3q96~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3q96", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3q96\| PDB=3q96 \| SCENE= }}

-	~~Authors: Sintchak, M.D., Aertgeerts, K., Yano, J.~~	+	===B-Raf kinase domain in complex with a tetrahydronaphthalene inhibitor===

-	~~Description~~: B-~~Raf kinase domain in complex with~~ a ~~tetrahydronaphthalene inhibitor~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21341678}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21341678 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21341678}}
		+
		+	==About this Structure==
		+	[[3q96]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q96 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:21341678</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Aertgeerts, K.]]
		+	[[Category: Sintchak, M D.]]
		+	[[Category: Yano, J.]]

OCA: Protected "3q96" [edit=sysop:move=sysop]

OCA — Wed, 19 Jan 2011 05:51:36 GMT

Protected "3q96" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:51, 19 January 2011

OCA: New page: '''Unreleased structure''' The entry 3q96 is ON HOLD Authors: Sintchak, M.D., Aertgeerts, K., Yano, J. Description: B-Raf kinase domain in complex with a tetrahydronaphthalene inhibito...

OCA — Wed, 19 Jan 2011 05:51:35 GMT

New page: '''Unreleased structure''' The entry 3q96 is ON HOLD Authors: Sintchak, M.D., Aertgeerts, K., Yano, J. Description: B-Raf kinase domain in complex with a tetrahydronaphthalene inhibito...

New page

'''Unreleased structure'''

The entry 3q96 is ON HOLD

Authors: Sintchak, M.D., Aertgeerts, K., Yano, J.

Description: B-Raf kinase domain in complex with a tetrahydronaphthalene inhibitor