2oho: Difference between revisions

Revision as of 10:56, 4 May 2008

Structural Basis for Glutamate Racemase Inhibitor

OverviewOverview

D-Glutamic acid is a required biosynthetic building block for peptidoglycan, and the enzyme glutamate racemase (GluR) catalyzes the inter-conversion of D and L-glutamate enantiomers. Therefore, GluR is considered as an attractive target for the design of new antibacterial drugs. Here, we report the crystal structures of GluR from Streptococcus pyogenes in both inhibitor-free and inhibitor-bound forms. The inhibitor free GluR crystallized in two different forms, which diffracted to 2.25 A and 2.5 A resolution, while the inhibitor-bound crystal diffracted to 2.5 A resolution. GluR is composed of two domains of alpha/beta protein that are related by pseudo-2-fold symmetry and the active site is located at the domain interface. The inhibitor, gamma-2-naphthylmethyl-D-glutamate, which was reported earlier as a novel potent competitive inhibitor, makes several hydrogen bonds with protein atoms, and the naphthyl moiety is located in the hydrophobic pocket. The inhibitor binding induces a disorder in one of the loops near the active site. In both crystal forms, GluR exists as a dimer and the interactions seen at the dimer interface are almost identical. This agrees well with the results from gel filtration and dynamic light-scattering studies.

About this StructureAbout this Structure

2OHO is a Single protein structure of sequence from Streptococcus pyogenes. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for glutamate racemase inhibition., Kim KH, Bong YJ, Park JK, Shin KJ, Hwang KY, Kim EE, J Mol Biol. 2007 Sep 14;372(2):434-43. Epub 2007 May 10. PMID:17658548 Page seeded by OCA on Sun May 4 10:56:37 2008

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OCA

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 [[Image:2oho.jpg|left|200px]]
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 '''Structural Basis for Glutamate Racemase Inhibitor'''
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 [[Category: Streptococcus pyogenes]]
 [[Category: Kim, E E.]]
-[[Category: isomerase]]
+[[Category: Isomerase]]
-[[Category: racemase]]
+[[Category: Racemase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 10:56:37 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:18:04 2008''