2jff: Difference between revisions

Revision as of 20:56, 18 December 2007

CRYSTAL STRUCTURE OF MURD LIGASE IN COMPLEX WITH D-GLU CONTAINING SULFONAMIDE INHIBITOR

OverviewOverview

Mur ligases play an essential role in the intracellular biosynthesis of, bacterial peptidoglycan, the main component of the bacterial cell wall, and represent attractive targets for the design of novel antibacterials., UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) catalyses the, addition of D-glutamic acid to the cytoplasmic intermediate, UDP-N-acetylmuramoyl-L-alanine (UMA) and is the second in the series of, Mur ligases. MurD ligase is highly stereospecific for its substrate, D-glutamic acid (D-Glu). Here, we report the high resolution crystal, structures of MurD in complexes with two novel inhibitors designed to, mimic the transition state of the reaction, which contain either the D-Glu, or the L-Glu moiety. The binding modes of N-sulfonyl-D-Glu and, N-sulfonyl-L-Glu derivatives were also characterised kinetically. The, results of this study represent an excellent starting point for further, development of novel inhibitors of this enzyme.

About this StructureAbout this Structure

2JFF is a Single protein structure of sequence from Escherichia coli with SO4 and LK2 as ligands. Active as UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase, with EC number 6.3.2.9 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Structural and functional characterization of enantiomeric glutamic acid derivatives as potential transition state analogue inhibitors of MurD ligase., Kotnik M, Humljan J, Contreras-Martel C, Oblak M, Kristan K, Herve M, Blanot D, Urleb U, Gobec S, Dessen A, Solmajer T, J Mol Biol. 2007 Jun 29;370(1):107-15. Epub 2007 May 4. PMID:17507028

Page seeded by OCA on Tue Dec 18 20:05:53 2007

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OCA

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 '''CRYSTAL STRUCTURE OF MURD LIGASE IN COMPLEX WITH D-GLU CONTAINING SULFONAMIDE INHIBITOR'''<br />
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 ==About this Structure==
-JFF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4 and LK2 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/UDP-N-acetylmuramoyl-L-alanine--D-glutamate_ligase UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.9 6.3.2.9] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JFF OCA].
+JFF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SO4 and LK2 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/UDP-N-acetylmuramoyl-L-alanine--D-glutamate_ligase UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.9 6.3.2.9] Known structural/functional Site: <scene name='pdbsite=AC1:So4 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JFF OCA].
 ==Reference==
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 [[Category: sulfonamide inhibitor]]
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