6uan - Revision history

OCA at 06:43, 11 April 2020

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OCA at 01:08, 7 March 2020

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OCA at 13:19, 18 December 2019

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OCA: Protected "6uan" [edit=sysop:move=sysop]

OCA — Wed, 23 Oct 2019 08:16:54 GMT

Protected "6uan" [edit=sysop:move=sysop]

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Revision as of 08:16, 23 October 2019

OCA: New page: ==B-Raf:14-3-3 complex== == Structural highlights ==
OCA — Wed, 23 Oct 2019 08:16:52 GMT

New page: ==B-Raf:14-3-3 complex== <StructureSection load='6uan' size='340' side='right'caption='6uan, resolution 3.90Å' scene=''> == Structural highlights == <table><tr><t...

New page

==B-Raf:14-3-3 complex==
<StructureSection load='6uan' size='340' side='right'caption='[[6uan]], [[Resolution|resolution]] 3.90Å' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6uan]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Spodoptera_aff._frugiperda_1_bold-2017 Spodoptera aff. frugiperda 1 bold-2017]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UAN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UAN FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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='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=6uan FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uan OCA], [http://pdbe.org/6uan PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uan RCSB], [http://www.ebi.ac.uk/pdbsum/6uan PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uan ProSAT]</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 ==
Raf kinases are important cancer drug targets. Paradoxically, many B-Raf inhibitors induce the activation of Raf kinases. Cryo-electron microscopy structural analysis of a phosphorylated B-Raf kinase domain dimer in complex with dimeric 14-3-3, at a resolution of ~3.9 angstroms, shows an asymmetric arrangement in which one kinase is in a canonical "active" conformation. The distal segment of the C-terminal tail of this kinase interacts with, and blocks, the active site of the cognate kinase in this asymmetric arrangement. Deletion of the C-terminal segment reduces Raf activity. The unexpected asymmetric quaternary architecture illustrates how the paradoxical activation of Raf by kinase inhibitors reflects an innate mechanism, with 14-3-3 facilitating inhibition of one kinase while maintaining activity of the other. Conformational modulation of these contacts may provide new opportunities for Raf inhibitor development.

Cryo-EM structure of a dimeric B-Raf:14-3-3 complex reveals asymmetry in the active sites of B-Raf kinases.,Kondo Y, Ognjenovic J, Banerjee S, Karandur D, Merk A, Kulhanek K, Wong K, Roose JP, Subramaniam S, Kuriyan J Science. 2019 Oct 4;366(6461):109-115. doi: 10.1126/science.aay0543. Epub 2019, Sep 19. PMID:31604311<ref>PMID:31604311</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6uan" style="background-color:#fffaf0;"></div>
== References ==
<references/>
TOC
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Spodoptera aff. frugiperda 1 bold-2017]]
[[Category: Banerjee, S]]
[[Category: Karandur, D]]
[[Category: Kondo, Y]]
[[Category: Kulhanek, K]]
[[Category: Kuriyan, J]]
[[Category: Merk, A]]
[[Category: Ognjenovic, J]]
[[Category: Roose, J P]]
[[Category: Subramaniam, S]]
[[Category: Wong, K]]
[[Category: Complex kinase]]
[[Category: Signaling protein]]