1yxx - Revision history

OCA at 09:01, 14 February 2024

OCA — Wed, 14 Feb 2024 09:01:00 GMT

←Older revision		Revision as of 09:01, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='1yxx' size='340' side='right'caption='[[1yxx]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1yxx' size='340' side='right'caption='[[1yxx]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1yxx]] is a 1 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=1YXX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1YXX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1yxx]] is a 1 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=1YXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YXX FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>~~, ~~<scene name='pdbligand=LI7:(3E)-3-~~[~~(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE'>LI7</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]] 2Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[~~[Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[1ywv\|1ywv]], [[1yxu\|1yxu]], [[1yxs\|1yxs]], [[1yxv\|1yxv]], [[1yxt\|1yxt]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=LI7:(3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE'>LI7</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</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=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [https://pdbe.org/1yxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [https://www.ebi.ac.uk/pdbsum/1yxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yxx ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Transferase Transferase], with EC number~~ [~~http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </~~span~~></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [~~http~~://pdbe.org/1yxx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1yxx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1yxx ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN]] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>	+	[https://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 22:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yxx ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yxx ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Pim1, a serine/threonine kinase, is involved in several biological functions including cell survival, proliferation, and differentiation. While pim1 has been shown to be involved in several hematopoietic cancers, it was also recently identified as a target of aberrant somatic hypermutation in diffuse large cell lymphoma (DLCL), the most common form of non-Hodgkin's lymphoma. The crystal structures of Pim1 in apo form and bound with AMPPNP have been solved and several unique features of Pim1 were identified, including the presence of an extra beta-hairpin in the N-terminal lobe and an unusual conformation of the hinge connecting the two lobes of the enzyme. While the apo Pim1 structure is nearly identical with that reported recently, the structure of AMPPNP bound to Pim1 is significantly different. Pim1 is unique among protein kinases due to the presence of a proline residue at position 123 that precludes the formation of the canonical second hydrogen bond between the hinge backbone and the adenine moiety of ATP. One crystal structure reported here shows that changing P123 to methionine, a common residue that offers the backbone hydrogen bond to ATP, does not restore the ATP binding pocket of Pim1 to that of a typical kinase. These unique structural features in Pim1 result in novel binding modes of AMP and a known kinase inhibitor scaffold, as shown by co-crystallography. In addition, the kinase activities of five Pim1 mutants identified in DLCL patients have been determined. In each case, the observed effects on kinase activity are consistent with the predicted consequences of the mutation on the Pim1 structure. Finally, 70 co-crystal structures of low molecular mass, low-affinity compounds with Pim1 have been solved in order to identify novel chemical classes as potential Pim1 inhibitors. Based on the structural information, opportunities for optimization of one specific example are discussed.
-
-	Crystal structures of proto-oncogene kinase Pim1: a target of aberrant somatic hypermutations in diffuse large cell lymphoma.,Kumar A, Mandiyan V, Suzuki Y, Zhang C, Rice J, Tsai J, Artis DR, Ibrahim P, Bremer R J Mol Biol. 2005 Apr 22;348(1):183-93. PMID:15808862<ref>PMID:15808862</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1yxx" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]		*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
-	*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]
	*[[3D structures of pim-1\|3D structures of pim-1]]		*[[3D structures of pim-1\|3D structures of pim-1]]
	== References ==		== References ==
Line 40:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Transferase]]~~	+	[[Category: Artis DR]]
-	[[Category: Artis~~, D R~~]]	+	[[Category: Bremer R]]
-	[[Category: Bremer, R]]	+	[[Category: Ibrahim P]]
-	[[Category: Ibrahim, P]]	+	[[Category: Kumar A]]
-	[[Category: Kumar, A]]	+	[[Category: Mandiyan V]]
-	[[Category: Mandiyan, V]]	+	[[Category: Rice J]]
-	[[Category: Rice, J]]	+	[[Category: Suzuki Y]]
-	[[Category: Suzuki, Y]]	+	[[Category: Tsai J]]
-	[[Category: Tsai, J]]	+	[[Category: Zhang C]]
-	[[Category: Zhang, C]]	+
-	~~[[Category: Ser/thr protein kinase~~]]	+

OCA at 08:55, 20 January 2021

OCA — Wed, 20 Jan 2021 08:55:02 GMT

←Older revision		Revision as of 08:55, 20 January 2021
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	==Crystal Structure of Kinase Pim1 in complex with (3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE==		==Crystal Structure of Kinase Pim1 in complex with (3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE==
-	<StructureSection load='1yxx' size='340' side='right' caption='[[1yxx]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='1yxx' size='340' side='right'caption='[[1yxx]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1yxx]] is a 1 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=1YXX OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1YXX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1yxx]] is a 1 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=1YXX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1YXX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=LI7:(3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE'>LI7</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=LI7:(3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE'>LI7</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ywv\|1ywv]], [[1yxu\|1yxu]], [[1yxs\|1yxs]], [[1yxv\|1yxv]], [[1yxt\|1yxt]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ywv\|1ywv]], [[1yxu\|1yxu]], [[1yxs\|1yxs]], [[1yxv\|1yxv]], [[1yxt\|1yxt]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([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">PIM1 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://pdbe.org/1yxx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yxx ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://pdbe.org/1yxx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yxx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 33:		Line 33:

	==See Also==		==See Also==
-	*[[~~Proto-oncogene serine~~/threonine-protein kinase\|~~Proto-oncogene serine~~/threonine-protein kinase]]	+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]		*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]
		+	*[[3D structures of pim-1\|3D structures of pim-1]]
	== References ==		== References ==
	<references/>		<references/>
Line 40:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Artis, D R]]		[[Category: Artis, D R]]

OCA at 06:57, 25 April 2018

OCA — Wed, 25 Apr 2018 06:57:55 GMT

←Older revision		Revision as of 06:57, 25 April 2018
Line 1:		Line 1:
		+
	==Crystal Structure of Kinase Pim1 in complex with (3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE==		==Crystal Structure of Kinase Pim1 in complex with (3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE==
	<StructureSection load='1yxx' size='340' side='right' caption='[[1yxx]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1yxx' size='340' side='right' caption='[[1yxx]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([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">PIM1 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://pdbe.org/1yxx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx 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=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://pdbe.org/1yxx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yxx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yx/1yxx_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yx/1yxx_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 09:30, 7 February 2016

OCA — Sun, 07 Feb 2016 09:30:29 GMT

←Older revision		Revision as of 09:30, 7 February 2016
Line 7:		Line 7:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([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">PIM1 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx 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=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://pdbe.org/1yxx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yxx ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	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 1yxx" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Proto-oncogene serine/threonine-protein kinase\|Proto-oncogene serine/threonine-protein kinase]]		*[[Proto-oncogene serine/threonine-protein kinase\|Proto-oncogene serine/threonine-protein kinase]]
		+	*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:04, 24 June 2015

OCA — Wed, 24 Jun 2015 07:04:31 GMT

←Older revision		Revision as of 07:04, 24 June 2015
Line 2:		Line 2:
	<StructureSection load='1yxx' size='340' side='right' caption='[[1yxx]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1yxx' size='340' side='right' caption='[[1yxx]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1yxx]] is a 1 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=1YXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YXX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1yxx]] is a 1 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=1YXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YXX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=LI7:(3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE'>LI7</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=LI7:(3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE'>LI7</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ywv\|1ywv]], [[1yxu\|1yxu]], [[1yxs\|1yxs]], [[1yxv\|1yxv]], [[1yxt\|1yxt]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ywv\|1ywv]], [[1yxu\|1yxu]], [[1yxs\|1yxs]], [[1yxv\|1yxv]], [[1yxt\|1yxt]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([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">PIM1 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </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=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx 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=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx PDBsum]</span></td></tr>
	</table>		</table>
Line 36:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Transferase]]
	[[Category: Artis, D R]]		[[Category: Artis, D R]]
	[[Category: Bremer, R]]		[[Category: Bremer, R]]
Line 48:		Line 48:
	[[Category: Zhang, C]]		[[Category: Zhang, C]]
	[[Category: Ser/thr protein kinase]]		[[Category: Ser/thr protein kinase]]
-	[[Category: Transferase]]

OCA at 14:03, 24 December 2014

OCA — Wed, 24 Dec 2014 14:03:37 GMT

←Older revision		Revision as of 14:03, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1yxx]] is a 1 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=1YXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YXX FirstGlance]. <br>		<table><tr><td colspan='2'>[[1yxx]] is a 1 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=1YXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YXX FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=LI7:(3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE'>LI7</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=LI7:(3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE'>LI7</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ywv\|1ywv]], [[1yxu\|1yxu]], [[1yxs\|1yxs]], [[1yxv\|1yxv]], [[1yxt\|1yxt]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ywv\|1ywv]], [[1yxu\|1yxu]], [[1yxs\|1yxs]], [[1yxv\|1yxv]], [[1yxt\|1yxt]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([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">PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx 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=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN]] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 36:		Line 38:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Artis, D R.]]	+	[[Category: Artis, D R]]
-	[[Category: Bremer, R.]]	+	[[Category: Bremer, R]]
-	[[Category: Ibrahim, P.]]	+	[[Category: Ibrahim, P]]
-	[[Category: Kumar, A.]]	+	[[Category: Kumar, A]]
-	[[Category: Mandiyan, V.]]	+	[[Category: Mandiyan, V]]
-	[[Category: Rice, J.]]	+	[[Category: Rice, J]]
-	[[Category: Suzuki, Y.]]	+	[[Category: Suzuki, Y]]
-	[[Category: Tsai, J.]]	+	[[Category: Tsai, J]]
-	[[Category: Zhang, C.]]	+	[[Category: Zhang, C]]
	[[Category: Ser/thr protein kinase]]		[[Category: Ser/thr protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 20:08, 29 September 2014

OCA — Mon, 29 Sep 2014 20:08:36 GMT

←Older revision		Revision as of 20:08, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1yxx.~~png~~\|~~left~~\|200px]]	+	==Crystal Structure of Kinase Pim1 in complex with (3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE==
		+	<StructureSection load='1yxx' size='340' side='right' caption='[[1yxx]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1yxx]] is a 1 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=1YXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YXX FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=LI7:(3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE'>LI7</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ywv\|1ywv]], [[1yxu\|1yxu]], [[1yxs\|1yxs]], [[1yxv\|1yxv]], [[1yxt\|1yxt]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PIM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1yxx RCSB], [http://www.ebi.ac.uk/pdbsum/1yxx PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yx/1yxx_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Pim1, a serine/threonine kinase, is involved in several biological functions including cell survival, proliferation, and differentiation. While pim1 has been shown to be involved in several hematopoietic cancers, it was also recently identified as a target of aberrant somatic hypermutation in diffuse large cell lymphoma (DLCL), the most common form of non-Hodgkin's lymphoma. The crystal structures of Pim1 in apo form and bound with AMPPNP have been solved and several unique features of Pim1 were identified, including the presence of an extra beta-hairpin in the N-terminal lobe and an unusual conformation of the hinge connecting the two lobes of the enzyme. While the apo Pim1 structure is nearly identical with that reported recently, the structure of AMPPNP bound to Pim1 is significantly different. Pim1 is unique among protein kinases due to the presence of a proline residue at position 123 that precludes the formation of the canonical second hydrogen bond between the hinge backbone and the adenine moiety of ATP. One crystal structure reported here shows that changing P123 to methionine, a common residue that offers the backbone hydrogen bond to ATP, does not restore the ATP binding pocket of Pim1 to that of a typical kinase. These unique structural features in Pim1 result in novel binding modes of AMP and a known kinase inhibitor scaffold, as shown by co-crystallography. In addition, the kinase activities of five Pim1 mutants identified in DLCL patients have been determined. In each case, the observed effects on kinase activity are consistent with the predicted consequences of the mutation on the Pim1 structure. Finally, 70 co-crystal structures of low molecular mass, low-affinity compounds with Pim1 have been solved in order to identify novel chemical classes as potential Pim1 inhibitors. Based on the structural information, opportunities for optimization of one specific example are discussed.

-	~~{{STRUCTURE_1yxx\| PDB=1yxx \| SCENE= }}~~	+	Crystal structures of proto-oncogene kinase Pim1: a target of aberrant somatic hypermutations in diffuse large cell lymphoma.,Kumar A, Mandiyan V, Suzuki Y, Zhang C, Rice J, Tsai J, Artis DR, Ibrahim P, Bremer R J Mol Biol. 2005 Apr 22;348(1):183-93. PMID:15808862<ref>PMID:15808862</ref>

-	~~===Crystal Structure~~ of ~~Kinase Pim1 in complex with (3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_15808862}}~~	+	==See Also==
-		+	*[[Proto-oncogene serine/threonine-protein kinase\|Proto-oncogene serine/threonine-protein kinase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~1yxx]] is a 1 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=1YXX OCA~~].	+	<references/>
-		+	__TOC__
-	==~~Reference~~==	+	</StructureSection>
-	<~~ref group="xtra">PMID:015808862<~~/~~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: Protected "1yxx" [edit=sysop:move=sysop]

OCA — Sat, 05 Jan 2013 17:39:43 GMT

Protected "1yxx" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:39, 5 January 2013

OCA at 17:39, 5 January 2013

OCA — Sat, 05 Jan 2013 17:39:41 GMT

←Older revision		Revision as of 17:39, 5 January 2013
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-	{{Seed}}
	[[Image:1yxx.png\|left\|200px]]		[[Image:1yxx.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_1yxx\| PDB=1yxx \| SCENE= }}		{{STRUCTURE_1yxx\| PDB=1yxx \| SCENE= }}

	===Crystal Structure of Kinase Pim1 in complex with (3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE===		===Crystal Structure of Kinase Pim1 in complex with (3E)-3-[(4-HYDROXYPHENYL)IMINO]-1H-INDOL-2(3H)-ONE===

-
-	<!--
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	{{ABSTRACT_PUBMED_15808862}}		{{ABSTRACT_PUBMED_15808862}}

	==About this Structure==		==About this Structure==
-	~~1YXX~~ is a 1 chain structure of 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=1YXX OCA].	+	[[1yxx]] is a 1 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=1YXX OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~15808862~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015808862</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
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	[[Category: Zhang, C.]]		[[Category: Zhang, C.]]
	[[Category: Ser/thr protein kinase]]		[[Category: Ser/thr protein kinase]]
-		+	[[Category: Transferase]]
-	~~''Page seeded by~~ [~~http~~:~~//oca.weizmann.ac.il/oca OCA~~ ] ~~on Mon Feb 16 12:54:07 2009''~~	+

OCA at 10:54, 16 February 2009

OCA — Mon, 16 Feb 2009 10:54:09 GMT

←Older revision		Revision as of 10:54, 16 February 2009
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	==About this Structure==		==About this Structure==
-	1YXX is a ~~[[Single protein]]~~ structure of 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=1YXX OCA].	+	1YXX is a 1 chain structure of 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=1YXX OCA].

	==Reference==		==Reference==
-	Crystal structures of proto-oncogene kinase Pim1: a target of aberrant somatic hypermutations in diffuse large cell lymphoma., Kumar A, Mandiyan V, Suzuki Y, Zhang C, Rice J, Tsai J, Artis DR, Ibrahim P, Bremer R, J Mol Biol. 2005 Apr 22;348(1):183-93. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/15808862 15808862]~~	+	<ref group="xtra">PMID:15808862</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Single protein]]
	[[Category: Artis, D R.]]		[[Category: Artis, D R.]]
	[[Category: Bremer, R.]]		[[Category: Bremer, R.]]
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	[[Category: Ser/thr protein kinase]]		[[Category: Ser/thr protein kinase]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun Jul 27 15~~:11:~~48 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 12:54:07 2009''