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4dq8

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4dq8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_marinum_M Mycobacterium marinum M]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DQ8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4dq8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_marinum_M Mycobacterium marinum M]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DQ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DQ8 FirstGlance]. <br>
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</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=4dq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dq8 OCA], [https://pdbe.org/4dq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dq8 RCSB], [https://www.ebi.ac.uk/pdbsum/4dq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dq8 ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dq8 OCA], [https://pdbe.org/4dq8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dq8 RCSB], [https://www.ebi.ac.uk/pdbsum/4dq8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dq8 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/ACKA_MYCMM ACKA_MYCMM]] Catalyzes the formation of acetyl phosphate from acetate and ATP. Can also catalyze the reverse reaction.[HAMAP-Rule:MF_00020]
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[https://www.uniprot.org/uniprot/ACKA_MYCMM ACKA_MYCMM] Catalyzes the formation of acetyl phosphate from acetate and ATP. Can also catalyze the reverse reaction.[HAMAP-Rule:MF_00020]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus "homolog-rescue" strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with &gt;55% overall sequence identity had active site Calpha RMSD &lt;1 A, &gt;85% side chain identity, and &gt;/=80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared &gt;55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases.
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Increasing the structural coverage of tuberculosis drug targets.,Baugh L, Phan I, Begley DW, Clifton MC, Armour B, Dranow DM, Taylor BM, Muruthi MM, Abendroth J, Fairman JW, Fox D 3rd, Dieterich SH, Staker BL, Gardberg AS, Choi R, Hewitt SN, Napuli AJ, Myers J, Barrett LK, Zhang Y, Ferrell M, Mundt E, Thompkins K, Tran N, Lyons-Abbott S, Abramov A, Sekar A, Serbzhinskiy D, Lorimer D, Buchko GW, Stacy R, Stewart LJ, Edwards TE, Van Voorhis WC, Myler PJ Tuberculosis (Edinb). 2014 Dec 19. pii: S1472-9792(14)20565-8. doi:, 10.1016/j.tube.2014.12.003. PMID:25613812<ref>PMID:25613812</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4dq8" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Mycobacterium marinum M]]
[[Category: Mycobacterium marinum M]]

Current revision

Crystal structure of acetate kinase AckA from Mycobacterium marinum

PDB ID 4dq8

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