Overview for MACiE Entry M0213
EC Number: 18.104.22.168 (A member of the Isomerases, Racemases and epimerases, Acting on amino acids and derivatives)
Enzyme Name: alanine racemase
Biological Species: Bacillus stearothermophilus (Bacteria)
Catalytic Chain UniprotKB Accession Codes:
Representative PDB Code: 1l6g - ALANINE RACEMASE BOUND WITH N-(5'-PHOSPHOPYRIDOXYL)-D-ALANINE (Resolution = 2.00 Å).
Catalytic CATH Codes:
"Other" CATH Codes:
Display structure information
Overall Comment: In the L-Ala to D-Ala direction (shown here) the tyrosine residue is known to be the catalytic base, in the reverse direction, the lysine is the catalytic base. The tyrosine and the lysine residues are on opposite sides of the PLP cofactor.
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Stepwise Description of the Reaction
|Step 1||The amine of the substrate L-alanine attacks the PLP cofactor in a nucleophilic addition and the bound Lys39 deprotonates the newly attached amine.|
|Step 2||The secondary amine that results from the initial attack initiates an elimination of the covalently bound lysine, resulting in free PLP and lysine in a neutral state.|
|Step 3||Tyr265B deprotonates the alpha carbon of the covalently bound intermediate, resulting in a carbanionic intermediate. Lys39 deprotonates water.|
|Step 4||Water deprotonates Tyr265B. The carbanionic intermediate deprotonates Lys39.|
|Step 5||The amine of Lys39 attacks the PLP in a nucleophilic addition reaction, the secondary amine of the attached substrate reprotonates from the bound Lys39|
|Step 6||The secondary amine that results from the initial attack initiates an elimination of the covalently bound product, resulting in D-alanine and the regenerated PLP cofactor.|
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Catalytic Residues Involved
||Location of Function
Organic Cofactors for M0213
- D. T. Major et al. (2006), J. Am. Chem. Soc., 128, 16345-16357. A combined quantum mechanical and molecular mechanical study of the reaction mechanism and alpha-amino acidity in alanine racemase.
- D. T. Major et al. (2006), J. Am. Chem. Soc., 128, 8114-8115. Transition state stabilization and alpha-amino carbon acidity in alanine racemase.
- M. A. Spies et al. (2007), J. Am. Chem. Soc., 129, 10678-10685. Intrinsic primary and secondary hydrogen kinetic isotope effects for alanine racemase from global analysis of progress curves.
- J. P. Shaw et al. (1997), Biochemistry, 36, 1329-1342. Determination of the structure of alanine racemase from Bacillus stearothermophilus at 1.9-A resolution.
- C. G. F. Stamper et al. (1998), Biochemistry, 37, 10438-10445. Reaction of alanine racemase with 1-aminoethylphosphonic acid forms a stable external aldimine.
- A. Watanabe et al. (2002), J. Biol. Chem., 277, 19166-19172. Reaction mechanism of alanine racemase from Bacillus stearothermophilus: x-ray crystallographic studies of the enzyme bound with N-(5'-phosphopyridoxyl)alanine.
- P. LeMagueres et al. (2005), Biochemistry, 44, 1471-1481. The 1.9 A crystal structure of alanine racemase from Mycobacterium tuberculosis contains a conserved entryway into the active site.
Homologue information for M0213 (1l6g)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
Links to this entry in other databases