4xv1: Difference between revisions
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The entry | ==B-Raf Kinase V600E oncogenic mutant in complex with PLX7904== | ||
<StructureSection load='4xv1' size='340' side='right'caption='[[4xv1]], [[Resolution|resolution]] 2.47Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4xv1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The March 2016 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Raf Protein Kinases'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2016_3 10.2210/rcsb_pdb/mom_2016_3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XV1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.47Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=904:N-(3-{[5-(2-CYCLOPROPYLPYRIMIDIN-5-YL)-1H-PYRROLO[2,3-B]PYRIDIN-3-YL]CARBONYL}-2,4-DIFLUOROPHENYL)-N-ETHYL-N-METHYLSULFURIC+DIAMIDE'>904</scene></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=4xv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xv1 OCA], [https://pdbe.org/4xv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xv1 RCSB], [https://www.ebi.ac.uk/pdbsum/4xv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xv1 ProSAT]</span></td></tr> | |||
</table> | |||
== 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> | |||
== 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. | |||
==See Also== | |||
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | |||
== References == | |||
[[Category: | <references/> | ||
[[Category: Zhang | __TOC__ | ||
[[Category: Zhang | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: RCSB PDB Molecule of the Month]] | |||
[[Category: Raf Protein Kinases]] | |||
[[Category: Zhang C]] | |||
[[Category: Zhang Y]] | |||