6f1x: Difference between revisions
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<StructureSection load='6f1x' size='340' side='right' caption='[[6f1x]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='6f1x' size='340' side='right' caption='[[6f1x]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6f1x]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F1X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F1X FirstGlance]. <br> | <table><tr><td colspan='2'>[[6f1x]] 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=6F1X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F1X FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C9Q:4-(3-chlorophenyl)-~{N}-ethyl-1~{H}-pyrrolo[2,3-b]pyridine-2-carboxamide'>C9Q</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C9Q:4-(3-chlorophenyl)-~{N}-ethyl-1~{H}-pyrrolo[2,3-b]pyridine-2-carboxamide'>C9Q</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NUDT1, MTH1 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6f1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f1x OCA], [http://pdbe.org/6f1x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f1x RCSB], [http://www.ebi.ac.uk/pdbsum/6f1x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f1x ProSAT]</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=6f1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f1x OCA], [http://pdbe.org/6f1x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f1x RCSB], [http://www.ebi.ac.uk/pdbsum/6f1x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f1x ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Andersson, M]] | [[Category: Andersson, M]] | ||
[[Category: Ericsson, U]] | [[Category: Ericsson, U]] | ||
Latest revision as of 09:58, 4 April 2018
Complex between MTH1 and compound 7 (a 7-azaindole-2-amide derivative)Complex between MTH1 and compound 7 (a 7-azaindole-2-amide derivative)
Structural highlights
Function[8ODP_HUMAN] Antimutagenic. Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress. Hydrolyzes 8-oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions. Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8-oxo-GTP and 8-oxo-ATP.[1] [2] [3] [4] [5] Publication Abstract from PubMedRecent literature has both suggested and questioned MTH1 as a novel cancer target. BAY-707 was just published as a target validation small molecule probe for assessing the effects of pharmacological inhibition of MTH1 on tumor cell survival, both in vitro and in vivo. (1) In this report, we describe the medicinal chemistry program creating BAY-707, where fragment-based methods were used to develop a series of highly potent and selective MTH1 inhibitors. Using structure-based drug design and rational medicinal chemistry approaches, the potency was increased over 10,000 times from the fragment starting point while maintaining high ligand efficiency and drug-like properties. Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design.,Rahm F, Viklund J, Tresaugues L, Ellermann M, Giese A, Ericsson U, Forsblom R, Ginman T, Gunther J, Hallberg K, Lindstrom J, Persson LB, Silvander C, Talagas A, Diaz-Saez L, Fedorov O, Huber KVM, Panagakou I, Siejka P, Gorjanacz M, Bauser M, Andersson M J Med Chem. 2018 Mar 7. doi: 10.1021/acs.jmedchem.7b01884. PMID:29485874[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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