1bd0

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{{STRUCTURE_1bd0| PDB=1bd0 | SCENE= }}
{{STRUCTURE_1bd0| PDB=1bd0 | SCENE= }}
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'''ALANINE RACEMASE COMPLEXED WITH ALANINE PHOSPHONATE'''
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===ALANINE RACEMASE COMPLEXED WITH ALANINE PHOSPHONATE===
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==Overview==
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(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.
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(as it appears on PubMed at http://www.pubmed.gov), where 9671513 is the PubMed ID number.
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{{ABSTRACT_PUBMED_9671513}}
==About this Structure==
==About this Structure==
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[[Category: Isomerase]]
[[Category: Isomerase]]
[[Category: Pyridoxal phosphate]]
[[Category: Pyridoxal phosphate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 18:51:58 2008''

Revision as of 15:52, 30 June 2008

Template:STRUCTURE 1bd0

ALANINE RACEMASE COMPLEXED WITH ALANINE PHOSPHONATE

Template:ABSTRACT PUBMED 9671513

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

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