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Overview for MACiE Entry M0066

Version history

General Information

EC Number: 2.6.1.21 (A member of the Transferases, Transferring nitrogenous groups, Transaminases)

Enzyme Name: D-alanine transaminase

Biological Species: Thermophilic bacterium ps3 (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P19938 - D-alanine aminotransferase

Representative PDB Code: 1daa - CRYSTALLOGRAPHIC STRUCTURE OF D-AMINO ACID AMINOTRANSFERASE COMPLEXED WITH PYRIDOXAL-5'-PHOSPHATE (Resolution = 1.94 Å).

Catalytic CATH Codes:

  • 3.30.470.10 - D-amino Acid Aminotransferase; Chain A, domain 1
  • 3.20.10.10 - D-amino Acid Aminotransferase, subunit A, domain 2

"Other" CATH Codes:

  • 3.30.470.10 - D-amino Acid Aminotransferase; Chain A, domain 1

Display structure information

Overall Reaction:

Image of D-glutamate

Image of pyruvate

right arrow

Image of 2-oxoglutarate

Image of D-alanine

D-glutamate
C00217
CHEBI:29986
pyruvate
C00022
CHEBI:15361
2-oxoglutarate
C00026
CHEBI:16810
D-alanine
C00133
CHEBI:57416

Overall Comment: This is a pyridoxal-phosphate (PLP) dependent enzyme. Leu201A is thought to play a crucial role in the transamination reaction by keeping the PLP in the correct orientation without disturbing its oscillating motion, this is especially important when the covalent bond is broken between the PLP and the Lys145.


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Stepwise Description of the Reaction

Step 1The amine of the substrate L-glutamate attacks the PLP cofactor in a nucleophilic addition and the bound Lys145 deprotonates the newly attached amine.
Step 2The 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 3Lys145 deprotonates the CH adjacent to the bound amine, resulting in double bond rearrangement as the PLP acts as an electron sink.
Step 4The PLP feeds the electrons back, resulting in the C=C attached to the aromatic ring deprotonates Lys145.
Step 5Lys145 deprotonates water, which initiates a nucleophilic attack on the carbon of the C=N group in an addition reaction.
Step 6The secondary amine deprotonates the attached hydroxyl group, initiating an elimination which releases 2-oxoglutarate.
Step 7The amine of PMP initiates a nucleophilic attack on the carbonyl carbon of pyruvate. The oxyanion deprotonates the newly formed secondary amine in the first step of a Schiff base formation.
Step 8The secondary amine initiates an elimination, forming the Schiff base and releasing water with concomitant deprotonation of Lys145.
Step 9Lys145 deprotonates the CH2 adjacent to the nitrogen, resulting in double bond rearrangement as the PLP acts as an electron sink.
Step 10The PLP feeds the electrons back, the N+=C bond deprotonates Lys145.
Step 11The amine of Lys145 attacks the PLP in a nucleophilic addition reaction, the secondary amine of the attached substrate reprotonates from the bound Lys145.
Step 12The secondary amine that results from the initial attack initiates an elimination of the covalently bound product, resulting in alanine and the regenerated PLP cofactor.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Tyr 31 A Side Chain
Lys 145 A Side Chain
Glu 177 A Side Chain
Leu 201 A Side Chain

Organic Cofactors for M0066

Type Identity Chain
Pyridoxal 5'-phosphate PLP 285 A Overview

References

  1. P. W. van Ophem et al. (1999), Biochemistry, 38, 1323-1331. Effects of the E177K mutation in D-amino acid transaminase. Studies on an essential coenzyme anchoring group that contributes to stereochemical fidelity.
    Medline: 9930994
  2. D. Peisach et al. (1998), Biochemistry, 37, 4958-4967. Crystallographic study of steps along the reaction pathway of D-amino acid aminotransferase.
    Medline: 9538014
  3. S. Surgio et al. (1998), Protein Eng., 11, 613-619. Crystal structures of L201A mutant of D-amino acid aminotransferase at 2.0 A resolution: implication of the structural role of Leu201 in transamination.
    Medline: 9749913

Homologue information for M0066 (1daa)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0305 aminodeoxychorismate lyase
4.1.3.38
1et0 3.30.470.10
3.20.10.10
0.78780.3985Compare

Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

GOA logo
catalytic activity (molecular function)
metabolic process (biological process)
transaminase activity (molecular function)
transferase activity (molecular function)
D-amino acid catabolic process (biological process)
pyridoxal phosphate binding (molecular function)
D-amino acid biosynthetic process (biological process)
D-alanine:2-oxoglutarate aminotransferase activity (molecular function)
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