1BD0

ALANINE RACEMASE COMPLEXED WITH ALANINE PHOSPHONATE

Summary for 1BD0

• Entry DOI: 10.2210/pdb1bd0/pdb
• Descriptor: ALANINE RACEMASE, {1-[(3-HYDROXY-METHYL-5-PHOSPHONOOXY-METHYL-PYRIDIN-4-YLMETHYL)-AMINO]-ETHYL}-PHOSPHONIC ACID (3 entities in total)
• Functional Keywords: alanine, isomerase, pyridoxal phosphate, alanine phosphonate
• Biological source: Geobacillus stearothermophilus
• Total number of polymer chains: 2
• Total formula weight: 87844.32

Authors

Stamper, G.F.,Morollo, A.A.,Ringe, D. (deposition date: 1998-05-12, release date: 1998-10-14, Last modification date: 2024-05-22)

Primary citation

Stamper, G.F.,Morollo, A.A.,Ringe, D.,Stamper, C.G.
Reaction of alanine racemase with 1-aminoethylphosphonic acid forms a stable external aldimine.
Biochemistry, 37:10438-10445, 1998

PubMed 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.

PubMed: 9671513
DOI: 10.1021/bi980692s

Experimental method

X-RAY DIFFRACTION (1.6 Å)