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Overview for MACiE Entry M0249

Version history

General Information

EC Number: 2.6.1.62 (A member of the Transferases, Transferring nitrogenous groups, Transaminases)

Enzyme Name: adenosylmethionine--8-amino-7-oxononanoate transaminase

Biological Species: Escherichia coli (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P12995 - Adenosylmethionine-8-amino-7-oxononanoate aminotransferase

Representative PDB Code: 1dty - CRYSTAL STRUCTURE OF ADENOSYLMETHIONINE-8-AMINO-7-OXONANOATEAMINOTRANSFERASE WITH PYRIDOXAL PHOSPHATE COFACTOR. (Resolution = 2.14 Å).

Catalytic CATH Codes:

  • 3.90.1150.10 - Aspartate Aminotransferase, domain 1
  • 3.40.640.10 - Type I PLP-dependent aspartate aminotransferase-like (Major domain)

"Other" CATH Codes:

  • 3.40.640.10 - Type I PLP-dependent aspartate aminotransferase-like (Major domain)
  • 3.90.1150.10 - Aspartate Aminotransferase, domain 1

Display structure information

Overall Reaction:

Image of 8-Amino-7-oxononanoate

Image of S-Adenosyl-L-methionine

right arrow

Image of 7,8-Diaminononanoate

Image of S-Adenosyl-4-methylthio-2-oxobutanoate

8-Amino-7-oxononanoate
C01092
CHEBI:12266
S-Adenosyl-L-methionine
C00019
CHEBI:59789
7,8-Diaminononanoate
C01037
CHEBI:17830
S-Adenosyl-4-methylthio-2-oxobutanoate
C04425
CHEBI:16490

Overall Comment: This enzyme catalyses the second of four steps in biotin biosynthesis and is the only known enzyme that utilises S-adenosylmethionine (SAM) as an amino donor. It is noted that S-adenosylhomocysteine can also act as donor. SAM is a costly metabolite, however, due to the fact that the aminotransferase-catalyzed reactions are most efficient when the pKa of the substrate and the enzyme are separated, SAM may be the only substrate available with an appropriate pKa [1].


View similar reactions


Stepwise Description of the Reaction

Step 1The amine of the substrate SAM attacks the PLP cofactor in a nucleophilic addition and the bound Lys274 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 3Lys274 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 Lys274.
Step 5Lys274 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 S-adenosyl-4-methylthio-2-oxobutanoate.
Step 7The amine of PMP initiates a nucleophilic attack on the carbonyl carbon of 8-amino-7-oxononanoate. 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 Lys274.
Step 9Lys274 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 Lys274.
Step 11The amine of Lys274 attacks the PLP in a nucleophilic addition reaction, the secondary amine of the attached substrate reprotonates from the bound Lys274.
Step 12The secondary amine that results from the initial attack initiates an elimination of the covalently bound product, resulting in 7,8-diaminononanoate and the regenerated PLP cofactor.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Asp 245 A Side Chain
Tyr 17 A Side Chain
Tyr 144 A Side Chain
Lys 274 A Side Chain

Organic Cofactors for M0249

Type Identity Chain
Pyridoxal 5'-phosphate PLP 450 A Overview

References

  1. A. C. Eliot et al. (2002), Biochemistry, 41, 12582-12589. The dual-specific active site of 7,8-diaminopelargonic acid synthase and the effect of the R391A mutation.
    Medline: 12379100
  2. J. Sandmark et al. (2004), Biochemistry, 43, 1213-1222. Conserved and nonconserved residues in the substrate binding site of 7,8-diaminopelargonic acid synthase from Escherichia coli are essential for catalysis.
    Medline: 14756557
  3. H. Kack et al. (1999), J. Mol. Biol., 291, 857-876. Crystal structure of diaminopelargonic acid synthase: evolutionary relationships between pyridoxal-5'-phosphate-dependent enzymes.
    Medline: 10452893

Homologue information for M0249 (1dty)

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
M0147 glycine hydroxymethyltransferase
2.1.2.1
1ls3 3.40.640.10
3.90.1150.10
0.76030.1125Compare
M0195 glutamate-1-semialdehyde 2,1-aminomutase
5.4.3.8
2gsa 3.40.640.10
3.90.1150.10
0.96980.3388Compare

View a comparison of the other reactions in MACiE with the CATH domain 3.40.640.10

View a comparison of the other reactions in MACiE with the CATH domain 3.90.1150.10


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)
adenosylmethionine-8-amino-7-oxononanoate transaminase activity (molecular function)
transaminase activity (molecular function)
biotin biosynthetic process (biological process)
pyridoxal phosphate binding (molecular function)
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