2q9j: Difference between revisions

Revision as of 19:37, 21 February 2008

Crystal structure of the C217S mutant of diaminopimelate epimerase

OverviewOverview

Diaminopimelate (DAP) epimerase catalyzes the stereoinversion of ll-DAP to meso-DAP, a precursor of l-lysine and an essential component of the bacterial peptidoglycan. This function is vital to bacteria and the enzyme therefore represents an attractive target for the design of novel anti-bacterials. DAP epimerase belongs to the group of PLP-independent amino acid racemases that function through a rather unusual mechanism involving two cysteines acting in concert as a base (thiolate) and an acid (thiol). We have solved the crystal structures of the apo-forms of DAP epimerase mutants (C73S and C217S) from Haemophilus influenzae at 2.3A and 2.2A resolution, respectively. These structures provide a snapshot of the enzyme in the first step of the catalytic cycle. Comparisons with the structures of the inhibitor-bound form reveal that the enzyme adopts an 'open conformation' in the absence of substrates or inhibitors with the two active site cysteines existing as a thiol-thiolate pair. Substrate binding to the C-terminal domain triggers the closure of the N-terminal domain coupled with tight encapsulation of the ligand, stabilization of the conformation of an active site loop containing Cys73 and expulsion of water molecules with concomitant desolvation of the thiolate base. This structural rearrangement is critical for catalysis.

About this StructureAbout this Structure

2Q9J is a Single protein structure of sequence from Haemophilus influenzae with and as ligands. Active as Diaminopimelate epimerase, with EC number 5.1.1.7 Full crystallographic information is available from OCA.

ReferenceReference

Dynamics of catalysis revealed from the crystal structures of mutants of diaminopimelate epimerase., Pillai B, Cherney M, Diaper CM, Sutherland A, Blanchard JS, Vederas JC, James MN, Biochem Biophys Res Commun. 2007 Nov 23;363(3):547-53. Epub 2007 Sep 17. PMID:17889830

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 ==Overview==
-Diaminopimelate (DAP) epimerase catalyzes the stereoinversion of ll-DAP to, meso-DAP, a precursor of l-lysine and an essential component of the, bacterial peptidoglycan. This function is vital to bacteria and the enzyme, therefore represents an attractive target for the design of novel, anti-bacterials. DAP epimerase belongs to the group of PLP-independent, amino acid racemases that function through a rather unusual mechanism, involving two cysteines acting in concert as a base (thiolate) and an acid, (thiol). We have solved the crystal structures of the apo-forms of DAP, epimerase mutants (C73S and C217S) from Haemophilus influenzae at 2.3A and, 2.2A resolution, respectively. These structures provide a snapshot of the, enzyme in the first step of the catalytic cycle. Comparisons with the, structures of the inhibitor-bound form reveal that the enzyme adopts an, 'open conformation' in the absence of substrates or inhibitors with the, two active site cysteines existing as a thiol-thiolate pair. Substrate, binding to the C-terminal domain triggers the closure of the N-terminal, domain coupled with tight encapsulation of the ligand, stabilization of, the conformation of an active site loop containing Cys73 and expulsion of, water molecules with concomitant desolvation of the thiolate base. This, structural rearrangement is critical for catalysis.
+Diaminopimelate (DAP) epimerase catalyzes the stereoinversion of ll-DAP to meso-DAP, a precursor of l-lysine and an essential component of the bacterial peptidoglycan. This function is vital to bacteria and the enzyme therefore represents an attractive target for the design of novel anti-bacterials. DAP epimerase belongs to the group of PLP-independent amino acid racemases that function through a rather unusual mechanism involving two cysteines acting in concert as a base (thiolate) and an acid (thiol). We have solved the crystal structures of the apo-forms of DAP epimerase mutants (C73S and C217S) from Haemophilus influenzae at 2.3A and 2.2A resolution, respectively. These structures provide a snapshot of the enzyme in the first step of the catalytic cycle. Comparisons with the structures of the inhibitor-bound form reveal that the enzyme adopts an 'open conformation' in the absence of substrates or inhibitors with the two active site cysteines existing as a thiol-thiolate pair. Substrate binding to the C-terminal domain triggers the closure of the N-terminal domain coupled with tight encapsulation of the ligand, stabilization of the conformation of an active site loop containing Cys73 and expulsion of water molecules with concomitant desolvation of the thiolate base. This structural rearrangement is critical for catalysis.
 ==About this Structure==
@@ Line 14: / Line 14: @@
 [[Category: Haemophilus influenzae]]
 [[Category: Single protein]]
-[[Category: Blanchard, J.S]]
+[[Category: Blanchard, J S]]
 [[Category: Cherney, M.]]
-[[Category: Diaper, C.M.]]
+[[Category: Diaper, C M.]]
 [[Category: Pillai, B]]
 [[Category: Sutherland, A.]]
-[[Category: Vederas, J.C.]]
+[[Category: Vederas, J C.]]
 [[Category: EDO]]
 [[Category: SO4]]
@@ Line 27: / Line 27: @@
 [[Category: two domains]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:44:25 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:37:25 2008''