1bd0
From Proteopedia
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==Overview== | ==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 ... | + | (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== | ==About this Structure== | ||
| - | 1BD0 is a | + | 1BD0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with IN5 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Alanine_racemase Alanine racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.1 5.1.1.1] Structure known Active Site: CIC. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1BD0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: pyridoxal phosphate]] | [[Category: pyridoxal phosphate]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:17:57 2007'' |
Revision as of 11:12, 5 November 2007
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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 with IN5 as ligand. Active as Alanine racemase, with EC number 5.1.1.1 Structure known Active Site: CIC. 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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