1znx: Difference between revisions
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< | ==Crystal Structure Of Mycobacterium tuberculosis Guanylate Kinase In Complex With GMP== | ||
<StructureSection load='1znx' size='340' side='right'caption='[[1znx]], [[Resolution|resolution]] 2.35Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1znx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZNX 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]] 2.35Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</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=1znx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1znx OCA], [https://pdbe.org/1znx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1znx RCSB], [https://www.ebi.ac.uk/pdbsum/1znx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1znx ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KGUA_MYCTU KGUA_MYCTU] Essential for recycling GMP and indirectly, cGMP (By similarity).[HAMAP-Rule:MF_00328] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zn/1znx_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1znx ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bacterial nucleoside monophosphate (NMP) kinases, which convert NMPs to nucleoside diphosphates (NDP), are investigated as potential antibacterial targets against pathogenic bacteria. Herein, we report the biochemical and structural characterization of GMP kinase from Mycobacterium tuberculosis (GMPKMt). GMPKMt is a monomer with an unusual specificity for ATP as a phosphate donor, a lower catalytic efficiency compared with eukaryotic GMPKs, and it carries two redox-sensitive cysteines in the central CORE domain. These properties were analyzed in the light of the high-resolution crystal structures of unbound, GMP-bound, and GDP-bound GMPKMt. The latter structure was obtained in both an oxidized form, in which the cysteines form a disulfide bridge, and a reduced form which is expected to correspond to the physiological enzyme. GMPKMt has a modular domain structure as most NMP kinases. However, it departs from eukaryotic GMPKs by the unusual conformation of its CORE domain, and by its partially open LID and GMP-binding domains which are the same in the apo-, GMP-bound, and GDP-bound forms. GMPKMt also features a unique GMP binding site which is less close-packed than that of mammalian GMPKs, and in which the replacement of a critical tyrosine by a serine removes a catalytic interaction. In contrast, the specificity of GMPKMt for ATP may be a general feature of GMPKs because of an invariant structural motif that recognizes the adenine base. Altogether, differences in domain dynamics and GMP binding between GMPKMt and mammalian GMPKs should reveal clues for the design of GMPKMt-specific inhibitors. | |||
Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate kinase.,Hible G, Christova P, Renault L, Seclaman E, Thompson A, Girard E, Munier-Lehmann H, Cherfils J Proteins. 2006 Feb 1;62(2):489-500. PMID:16288457<ref>PMID:16288457</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1znx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Guanylate kinase 3D structures|Guanylate kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
[[Category: | |||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Cherfils J]] | |||
[[Category: Cherfils | [[Category: Christova P]] | ||
[[Category: Christova | [[Category: Girard E]] | ||
[[Category: Girard | [[Category: Hible G]] | ||
[[Category: Hible | [[Category: Munier-Lehmann H]] | ||
[[Category: Munier-Lehmann | [[Category: Renault L]] | ||
[[Category: Renault | [[Category: Seclaman E]] | ||
[[Category: Seclaman | [[Category: Thompson A]] | ||
[[Category: Thompson | |||
Latest revision as of 11:58, 6 November 2024
Crystal Structure Of Mycobacterium tuberculosis Guanylate Kinase In Complex With GMPCrystal Structure Of Mycobacterium tuberculosis Guanylate Kinase In Complex With GMP
Structural highlights
FunctionKGUA_MYCTU Essential for recycling GMP and indirectly, cGMP (By similarity).[HAMAP-Rule:MF_00328] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBacterial nucleoside monophosphate (NMP) kinases, which convert NMPs to nucleoside diphosphates (NDP), are investigated as potential antibacterial targets against pathogenic bacteria. Herein, we report the biochemical and structural characterization of GMP kinase from Mycobacterium tuberculosis (GMPKMt). GMPKMt is a monomer with an unusual specificity for ATP as a phosphate donor, a lower catalytic efficiency compared with eukaryotic GMPKs, and it carries two redox-sensitive cysteines in the central CORE domain. These properties were analyzed in the light of the high-resolution crystal structures of unbound, GMP-bound, and GDP-bound GMPKMt. The latter structure was obtained in both an oxidized form, in which the cysteines form a disulfide bridge, and a reduced form which is expected to correspond to the physiological enzyme. GMPKMt has a modular domain structure as most NMP kinases. However, it departs from eukaryotic GMPKs by the unusual conformation of its CORE domain, and by its partially open LID and GMP-binding domains which are the same in the apo-, GMP-bound, and GDP-bound forms. GMPKMt also features a unique GMP binding site which is less close-packed than that of mammalian GMPKs, and in which the replacement of a critical tyrosine by a serine removes a catalytic interaction. In contrast, the specificity of GMPKMt for ATP may be a general feature of GMPKs because of an invariant structural motif that recognizes the adenine base. Altogether, differences in domain dynamics and GMP binding between GMPKMt and mammalian GMPKs should reveal clues for the design of GMPKMt-specific inhibitors. Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate kinase.,Hible G, Christova P, Renault L, Seclaman E, Thompson A, Girard E, Munier-Lehmann H, Cherfils J Proteins. 2006 Feb 1;62(2):489-500. PMID:16288457[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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