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1mrn

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Revision as of 18:37, 20 November 2019

CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE COMPLEXED WITH BISUBSTRATE INHIBITOR (TP5A)

Structural highlights

1mrn is a 1 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, 1mrs
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

The chemical synthesis of new compounds designed as inhibitors of Mycobacterium tuberculosis TMP kinase (TMPK) is reported. The synthesis concerns TMP analogues modified at the 5-position of the thymine ring as well as a novel compound with a six-membered sugar ring. The binding properties of the analogues are compared with the known inhibitor azido-TMP, which is postulated here to work by excluding the TMP-bound Mg(2+) ion. The crystallographic structure of the complex of one of the compounds, 5-CH(2)OH-dUMP, with TMPK has been determined at 2.0 A. It reveals a major conformation for the hydroxyl group in contact with a water molecule and a minor conformation pointing toward Ser(99). Looking for a role for Ser(99), we have identified an unusual catalytic triad, or a proton wire, made of strictly conserved residues (including Glu(6), Ser(99), Arg(95), and Asp(9)) that probably serves to protonate the transferred PO(3) group. The crystallographic structure of the commercially available bisubstrate analogue P(1)-(adenosine-5')-P(5)-(thymidine-5')-pentaphosphate bound to TMPK is also reported at 2.45 A and reveals an alternative binding pocket for the adenine moiety of the molecule compared with what is observed either in the Escherichia coli or in the yeast enzyme structures. This alternative binding pocket opens a way for the design of a new family of specific inhibitors.

Enzymatic and structural analysis of inhibitors designed against Mycobacterium tuberculosis thymidylate kinase. New insights into the phosphoryl transfer mechanism.,Haouz A, Vanheusden V, Munier-Lehmann H, Froeyen M, Herdewijn P, Van Calenbergh S, Delarue M J Biol Chem. 2003 Feb 14;278(7):4963-71. Epub 2002 Nov 25. PMID:12454011^[1]

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

References

↑ Haouz A, Vanheusden V, Munier-Lehmann H, Froeyen M, Herdewijn P, Van Calenbergh S, Delarue M. Enzymatic and structural analysis of inhibitors designed against Mycobacterium tuberculosis thymidylate kinase. New insights into the phosphoryl transfer mechanism. J Biol Chem. 2003 Feb 14;278(7):4963-71. Epub 2002 Nov 25. PMID:12454011 doi:10.1074/jbc.M209630200

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/1mrn"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE COMPLEXED WITH BISUBSTRATE INHIBITOR (TP5A)==
-<StructureSection load='1mrn' size='340' side='right' caption='[[1mrn]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
+<StructureSection load='1mrn' size='340' side='right'caption='[[1mrn]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1mrn]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MRN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MRN FirstGlance]. <br>
@@ Line 30: / Line 30: @@
 </div>
 <div class="pdbe-citations 1mrn" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Thymidylate kinase|Thymidylate kinase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: DTMP kinase]]
 [[Category: Calenbergh, S Van]]

1mrn

From Proteopedia

Revision as of 18:37, 20 November 2019

CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE COMPLEXED WITH BISUBSTRATE INHIBITOR (TP5A)

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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