6ziz
From Proteopedia
(Difference between revisions)
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==CRYSTAL STRUCTURE OF NRAS Q61R IN COMPLEX WITH GTP AND COMPOUND 18== | ==CRYSTAL STRUCTURE OF NRAS Q61R IN COMPLEX WITH GTP AND COMPOUND 18== | ||
| - | <StructureSection load='6ziz' size='340' side='right'caption='[[6ziz]]' scene=''> | + | <StructureSection load='6ziz' size='340' side='right'caption='[[6ziz]], [[Resolution|resolution]] 1.79Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZIZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZIZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ziz]] 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=6ZIZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZIZ FirstGlance]. <br> |
| - | </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=6ziz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ziz OCA], [http://pdbe.org/6ziz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ziz RCSB], [http://www.ebi.ac.uk/pdbsum/6ziz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ziz ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EZZ:(3~{S})-3-[2-[(dimethylamino)methyl]-1~{H}-indol-3-yl]-5-oxidanyl-2,3-dihydroisoindol-1-one'>EZZ</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NRAS, HRAS1 ([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'>[http://proteopedia.org/fgij/fg.htm?mol=6ziz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ziz OCA], [http://pdbe.org/6ziz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ziz RCSB], [http://www.ebi.ac.uk/pdbsum/6ziz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ziz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/RASN_HUMAN RASN_HUMAN]] Defects in NRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Defects in NRAS are the cause of Noonan syndrome type 6 (NS6) [MIM:[http://omim.org/entry/613224 613224]]. A syndrome 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:19966803</ref> Defects in NRAS are the cause of autoimmune lymphoproliferative syndrome type 4 (ALPS4) [MIM:[http://omim.org/entry/614470 614470]]. A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies.<ref>PMID:17517660</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/RASN_HUMAN RASN_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Activating mutations in the three human RAS genes, KRAS, NRAS and HRAS, are among the most common oncogenic drivers in human cancers. Covalent KRAS(G12C) inhibitors, which bind to the switch II pocket in the 'off state' of KRAS, represent the first direct KRAS drugs that entered human clinical trials. However, the remaining 85% of non-KRAS(G12C)-driven cancers remain undrugged as do NRAS and HRAS and no drugs targeting the 'on state' have been discovered so far. The switch I/II pocket is a second pocket for which the nanomolar inhibitor BI-2852 has been discovered. Here, we elucidate inhibitor binding modes in KRAS, NRAS and HRAS on and off and discuss future strategies to drug all RAS isoforms with this one pocket. | ||
| + | |||
| + | Drugging all RAS isoforms with one pocket.,Kessler D, Bergner A, Bottcher J, Fischer G, Dobel S, Hinkel M, Mullauer B, Weiss-Puxbaum A, McConnell DB Future Med Chem. 2020 Aug 11. doi: 10.4155/fmc-2020-0221. PMID:32779487<ref>PMID:32779487</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ziz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Boettcher J]] | + | [[Category: Boettcher, J]] |
| - | [[Category: Fischer G]] | + | [[Category: Fischer, G]] |
| - | [[Category: Kessler D]] | + | [[Category: Kessler, D]] |
| + | [[Category: Gtpase]] | ||
| + | [[Category: Hydrolase]] | ||
Revision as of 07:14, 25 November 2020
CRYSTAL STRUCTURE OF NRAS Q61R IN COMPLEX WITH GTP AND COMPOUND 18
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Categories: Human | Large Structures | Boettcher, J | Fischer, G | Kessler, D | Gtpase | Hydrolase
