1bd0
From Proteopedia
ALANINE RACEMASE COMPLEXED WITH ALANINE PHOSPHONATE
Overview
(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.
About this Structure
1BD0 is a Single protein structure of sequence from Geobacillus stearothermophilus. Full crystallographic information is available from OCA.
Reference
Reaction of alanine racemase with 1-aminoethylphosphonic acid forms a stable external aldimine., Stamper GF, Morollo AA, Ringe D, Biochemistry. 1998 Jul 21;37(29):10438-45. PMID:9671513 Page seeded by OCA on Fri May 2 11:21:22 2008
