PDBsum entry 1bd0

Isomerase

PDB id: 1bd0

Contents

Protein chains

381 a.a. *

Ligands

IN5 ×2

Waters ×387

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Reaction of alanine racemase with 1-Aminoethylphosphonic acid forms a stable external aldimine.
• Authors: G.F.Stamper, A.A.Morollo, D.Ringe, C.G.Stamper.
• Ref.: Biochemistry, 1998, 37, 10438-10445. [DOI no: 10.1021/bi980692s]
• PubMed id: 9671513

Abstract

(R)-1-Aminoethylphosphonic acid (L-Ala-P), a synthetic L-alanine analogue, has antibacterial activity and is a time-dependent inactivator of all purified Gram-positive bacterial alanine racemases that have been tested. L-Ala-P forms an external aldimine with the bound pyridoxal 5'-phosphate (PLP) cofactor, but is neither racemized nor efficiently hydrolyzed. To understand the structural basis of the inactivation of the enzyme by L-Ala-P, we determined the crystal structure of the complex between L-Ala-P and alanine racemase at 1.6 A resolution. The cofactor derivative in the inhibited structure tilts outward from the protein approximately 20 degrees relative to the internal aldimine. The phosphonate oxygens are within hydrogen bonding distance of four amino acid residues and two water molecules in the active site of the enzyme. L-Ala-P is an effective inhibitor of alanine racemase because, upon formation of the external aldimine, the phosphonate group interacts with putative catalytic residues, thereby rendering them unavailable for catalysis. Furthermore, this aldimine appears to be inappropriately aligned for efficient Calpha proton abstraction. The combination of these effects leads to a stable aldimine derivative and potent inactivation of alanine racemase by this compound.

Secondary reference #1

• Title: Determination of the structure of alanine racemase from bacillus stearothermophilus at 1.9-A resolution.
• Authors: J.P.Shaw, G.A.Petsko, D.Ringe.
• Ref.: Biochemistry, 1997, 36, 1329-1342. [DOI no: 10.1021/bi961856c]
• PubMed id: 9063881

Secondary reference #2

• Title: X-Ray crystallographic studies of the alanine-Specific racemase from bacillus stearothermophilus. Overproduction, Crystallization, And preliminary characterization.
• Authors: D.J.Neidhart, M.D.Distefano, K.Tanizawa, K.Soda, C.T.Walsh, G.A.Petsko.
• Ref.: J Biol Chem, 1987, 262, 15323-15326.
• PubMed id: 3680197