1w2g

From Proteopedia

(Difference between revisions)

Revision as of 07:12, 4 April 2018

Crystal Structure Of Mycobacterium Tuberculosis Thymidylate Kinase Complexed With Deoxythymidine (dT) (2.1 A Resolution)

Structural highlights

1w2g is a 2 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1g3u, 1gsi, 1gtv, 1mrn, 1mrs, 1n5i, 1n5j, 1n5k, 1n5l, 1w2h
Activity:	dTMP kinase, with EC number 2.7.4.9
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KTHY_MYCTU] Catalyzes the reversible phosphorylation of deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), using ATP as its preferred phosphoryl donor. Situated at the junction of both de novo and salvage pathways of deoxythymidine triphosphate (dTTP) synthesis, is essential for DNA synthesis and cellular growth. Has a broad specificity for nucleoside triphosphates, being highly active with ATP or dATP as phosphate donors, and less active with ITP, GTP, CTP and UTP.[HAMAP-Rule:MF_00165]

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 PubMed

Tuberculosis (TB) is the primary cause of mortality among infectious diseases. Mycobacterium tuberculosis thymidylate kinase (TMPK(Mtub)) catalyzes the ATP-dependent phosphorylation of deoxythymidine 5'-monophosphate (dTMP). Essential to DNA replication, this enzyme represents a promising target for developing new drugs against TB, because the configuration of its active site is unique within the TMPK family. Indeed, it has been proposed that, as opposed to other TMPKs, catalysis by TMPK(Mtub) necessitates the transient binding of a magnesium ion coordinating the phosphate acceptor. Moreover, 3'-azidodeoxythymidine monophosphate (AZTMP) is a competitive inhibitor of TMPK(Mtub), whereas it is a substrate for human and other TMPKs. Here, the crystal structures of TMPK(Mtub) in complex with deoxythymidine (dT) and AZTMP were determined to 2.1 and 2.0 A resolution, respectively, and suggest a mechanism for inhibition. The azido group of AZTMP perturbs the induced-fit mechanism normally adopted by the enzyme. Magnesium is prevented from binding, and the resulting electrostatic environment precludes phosphoryl transfer from occurring. Our data provide a model for drug development against tuberculosis.

The crystal structure of Mycobacterium tuberculosis thymidylate kinase in complex with 3'-azidodeoxythymidine monophosphate suggests a mechanism for competitive inhibition.,Fioravanti E, Adam V, Munier-Lehmann H, Bourgeois D Biochemistry. 2005 Jan 11;44(1):130-7. PMID:15628853^[1]

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

References

↑ Fioravanti E, Adam V, Munier-Lehmann H, Bourgeois D. The crystal structure of Mycobacterium tuberculosis thymidylate kinase in complex with 3'-azidodeoxythymidine monophosphate suggests a mechanism for competitive inhibition. Biochemistry. 2005 Jan 11;44(1):130-7. PMID:15628853 doi:10.1021/bi0484163

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1w2g"

@@ Line 1: / Line 1: @@
-==CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE COMPLEXED WITH DEOXYTHYMIDINE (DT) (2.1 A RESOLUTION)==
+==Crystal Structure Of Mycobacterium Tuberculosis Thymidylate Kinase Complexed With Deoxythymidine (dT) (2.1 A Resolution)==
 <StructureSection load='1w2g' size='340' side='right' caption='[[1w2g]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1g3u|1g3u]], [[1gsi|1gsi]], [[1gtv|1gtv]], [[1mrn|1mrn]], [[1mrs|1mrs]], [[1n5i|1n5i]], [[1n5j|1n5j]], [[1n5k|1n5k]], [[1n5l|1n5l]], [[1w2h|1w2h]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </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=1w2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w2g OCA], [http://pdbe.org/1w2g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w2g RCSB], [http://www.ebi.ac.uk/pdbsum/1w2g PDBsum]</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=1w2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w2g OCA], [http://pdbe.org/1w2g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w2g RCSB], [http://www.ebi.ac.uk/pdbsum/1w2g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1w2g ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w2/1w2g_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w2/1w2g_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1w2g

From Proteopedia

Revision as of 07:12, 4 April 2018

Crystal Structure Of Mycobacterium Tuberculosis Thymidylate Kinase Complexed With Deoxythymidine (dT) (2.1 A Resolution)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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