6p9m: Difference between revisions

Revision as of 06:35, 3 June 2020

Crystal structure of Mycobacterium tuberculosis KasA in complex with O6J

Structural highlights

6p9m is a 1 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	GOL, IPA, NA, O6J
Gene:	kasA, Rv2245, MTCY427.26 (MYCTU)
Activity:	[acyl-carrier-protein_synthase_I Beta-ketoacyl-[acyl-carrier-protein] synthase I], with EC number 2.3.1.41
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FAB1_MYCTU] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP (By similarity).

Publication Abstract from PubMed

Published Mycobacterium tuberculosis beta-ketoacyl-ACP synthase KasA inhibitors lack sufficient potency and/or pharmacokinetic properties. A structure-based approach was used to optimize existing KasA inhibitor DG167. This afforded indazole JSF-3285 with a 30-fold increase in mouse plasma exposure. Biochemical, genetic, and X-ray studies confirmed JSF-3285 targets KasA. JSF-3285 offers substantial activity in an acute mouse model of infection and in the corresponding chronic infection model, with efficacious reductions in colony-forming units at doses as low as 5 mg/kg once daily orally and improvement of the efficacy of front-line drugs isoniazid or rifampicin. JSF-3285 is a promising preclinical candidate for tuberculosis.

A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA.,Inoyama D, Awasthi D, Capodagli GC, Tsotetsi K, Sukheja P, Zimmerman M, Li SG, Jadhav R, Russo R, Wang X, Grady C, Richmann T, Shrestha R, Li L, Ahn YM, Ho Liang HP, Mina M, Park S, Perlin DS, Connell N, Dartois V, Alland D, Neiditch MB, Kumar P, Freundlich JS Cell Chem Biol. 2020 Mar 19. pii: S2451-9456(20)30071-4. doi:, 10.1016/j.chembiol.2020.02.007. PMID:32197094^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Inoyama D, Awasthi D, Capodagli GC, Tsotetsi K, Sukheja P, Zimmerman M, Li SG, Jadhav R, Russo R, Wang X, Grady C, Richmann T, Shrestha R, Li L, Ahn YM, Ho Liang HP, Mina M, Park S, Perlin DS, Connell N, Dartois V, Alland D, Neiditch MB, Kumar P, Freundlich JS. A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA. Cell Chem Biol. 2020 Mar 19. pii: S2451-9456(20)30071-4. doi:, 10.1016/j.chembiol.2020.02.007. PMID:32197094 doi:https://dx.doi.org/10.1016/j.chembiol.2020.02.007

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Inoyama D, Awasthi D, Capodagli GC, Tsotetsi K, Sukheja P, Zimmerman M, Li SG, Jadhav R, Russo R, Wang X, Grady C, Richmann T, Shrestha R, Li L, Ahn YM, Ho Liang HP, Mina M, Park S, Perlin DS, Connell N, Dartois V, Alland D, Neiditch MB, Kumar P, Freundlich JS. A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA. Cell Chem Biol. 2020 Mar 19. pii: S2451-9456(20)30071-4. doi:, 10.1016/j.chembiol.2020.02.007. PMID:32197094 doi:https://dx.doi.org/10.1016/j.chembiol.2020.02.007

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='6p9m' size='340' side='right'caption='[[6p9m]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6p9m]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P9M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P9M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6p9m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6P9M OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6P9M FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=O6J:N-(2-cyano-3-methyl-1H-indol-5-yl)pentane-1-sulfonamide'>O6J</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=O6J:N-(2-cyano-3-methyl-1H-indol-5-yl)pentane-1-sulfonamide'>O6J</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">kasA, Rv2245, MTCY427.26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-ketoacyl-[acyl-carrier-protein]_synthase_I Beta-ketoacyl-[acyl-carrier-protein] synthase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] </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=6p9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p9m OCA], [http://pdbe.org/6p9m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p9m RCSB], [http://www.ebi.ac.uk/pdbsum/6p9m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p9m 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=6p9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p9m OCA], [http://pdbe.org/6p9m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p9m RCSB], [http://www.ebi.ac.uk/pdbsum/6p9m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p9m ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: Large Structures]]
+[[Category: Myctu]]
 [[Category: Capodagli, G C]]
 [[Category: Neiditch, M B]]

6p9m: Difference between revisions

Revision as of 06:35, 3 June 2020

Crystal structure of Mycobacterium tuberculosis KasA in complex with O6J

Structural highlights

Function

Publication Abstract from PubMed

References

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