PDBsum entry: 1zuw

Isomerase

PDB id: 1zuw

Contents

Protein chains

261 a.a. *

Ligands

DGL ×3

Waters ×805

* Residue conservation analysis

PDB id:

1zuw

Name:

Isomerase

Title:

Crystal structure of b.Subtilis glutamate racemase (race) wi

Structure:

Glutamate racemase 1. Chain: a, b, c. Engineered: yes

Source:

Bacillus subtilis. Organism_taxid: 1423. Gene: race. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

1.75Å R-factor: 0.179 R-free: 0.237

Authors:

S.N.Ruzheinikov,M.A.Taal,S.E.Sedelnikova,P.J.Baker,D.W.Rice

Key ref:

S.N.Ruzheinikov et al. (2005). Substrate-induced conformational changes in Bacillus subtilis glutamate racemase and their implications for drug discovery. Structure (Camb), 13, 1707-1713. PubMed id: 16271894 DOI: 10.1016/j.str.2005.07.024

Date:

01-Jun-05 Release date: 06-Dec-05

Protein chains

P94556  (MURI1_BACSU) -  Glutamate racemase 1

Seq: 272 a.a.

Struc: 261 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.5.1.1.3 - Glutamate racemase.
• Reaction: L-glutamate = D-glutamate

L-glutamate (Bound ligand (Het Group name = DGL) corresponds exactly) = D-glutamate

• Cofactor: Pyridoxal 5'-phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: metabolic process (4 terms)
• Biochemical function: isomerase activity (3 terms)

reference

DOI no: 10.1016/j.str.2005.07.024

Structure (Camb) 13:1707-1713 (2005)

PubMed id: 16271894

Substrate-induced conformational changes in Bacillus subtilis glutamate racemase and their implications for drug discovery.

S.N.Ruzheinikov, M.A.Taal, S.E.Sedelnikova, P.J.Baker, D.W.Rice.

ABSTRACT

D-glutamate is an essential building block of the peptidoglycan layer in bacterial cell walls and can be synthesized from L-glutamate by glutamate racemase (RacE). The structure of a complex of B. subtilis RacE with D-glutamate reveals that the glutamate is buried in a deep pocket, whose formation at the interface of the enzyme's two domains involves a large-scale conformational rearrangement. These domains are related by pseudo-2-fold symmetry, which superimposes the two catalytic cysteine residues, which are located at equivalent positions on either side of the alpha carbon of the substrate. The structural similarity of these two domains suggests that the racemase activity of RacE arose as a result of gene duplication. The structure of the complex is dramatically different from that proposed previously and provides new insights into the RacE mechanism and an explanation for the potency of a family of RacE inhibitors, which have been developed as novel antibiotics.

Selected figure(s)

Figure 2.
Figure 2. Structure/Function Relationships of B. subtilis RacE
(A) The topology of the secondary structure elements of B. subtilis RacE. b strands are represented by arrows, and a helices lying above and below the plane of the b sheet are shown as unshaded and shaded cylinders, respectively. The approximate position of the pseudo-2-fold axis that relates the enzyme's two domains is shown by the diad.
(B) A schematic diagram of the dimer of B. subtilis RacE with helices and strands in one subunit numbered and colored red and blue, respectively, and the 2-fold-related subunit colored green. The position of the bound glutamate is shown in CPK format.
(C) A schematic diagram illustrating the different modes of dimerization of B. subtilis RacE (green), A. pyrophilus MurI (blue), and P. horikoshii AspR (red). One subunit of each enzyme was superimposed to reveal the different position of the 2-fold-related subunits.
(D) A stereodiagram of the final 2F[o] - F[c] map calculated at 1.75 Å and showing the location of the enzyme bound D-Glu.
(E) The two domains of RacE are shown superimposed (domain I in bronze with red glutamate and domain II in green with green glutamate) in a schematic diagram that also shows the relative position of the glutamate moiety (stick format) with respect to the catalytic cysteines.
(F) A stereodiagram of the substrate binding site in the RacE/D-Glu binary complex. Residues that lie close to the D-Glu are shown in a ball-and-stick format. The path of the protein chain is shown as a worm. Red spheres show water molecules. Hydrogen bond contacts made between the D-Glu and either the enzyme or enzyme bound waters are shown as dotted lines.
(G) A schematic stereorepresentation of the superposed structures of the B. subtilis RacE/glutamate complex (green) and the A. pyrophilus MurI/glutamine complex (blue). The elements of secondary structure in the B. subtilis enzyme are identified. The position of the bound glutamate in B. subtilis RacE is shown in CPK format, and the structural changes that accompany substrate binding can be seen.
(H) Stereodiagram indicating the modeled positions of the 4S and 4R isomers of 4-substituted D-glutamic acid inhibitors of RacE. The hydrophobic substituent in the 4S isomer (labeled) can be seen to lie in a pocket bounded by a cluster of largely hydrophobic side chains. The entrance to the pocket is partially occluded by Val149. The position of the hydrophobic substituent in the 4R isomer is such that it appears to form adverse contacts with the side chains of Cys40 and Glu153.

The above figure is reprinted by permission from Cell Press: Structure (Camb) (2005, 13, 1707-1713) copyright 2005.

Figure was selected by an automated process.