spacer

Overview for MACiE Entry M0283

Version history

General Information

EC Number: 2.6.1.85 (A member of the Transferases, Transferring nitrogenous groups, Transaminases)

Enzyme Name: aminodeoxychorismate synthase

Biological Species: Escherichia coli (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P05041 - Para-aminobenzoate synthase component 1

Representative PDB Code: 1k0g - THE CRYSTAL STRUCTURE OF AMINODEOXYCHORISMATE SYNTHASE FROMPHOSPHATE GROWN CRYSTALS (Resolution = 2.05 Å).

Catalytic CATH Codes:

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of chorismate

Image of Glutamine

right arrow

Image of glutamate

Image of 4-amino 4-deoxychlorismate

chorismate
C00251
CHEBI:29748
Glutamine
C00064
CHEBI:58359
glutamate
C00025
CHEBI:16015
4-amino 4-deoxychlorismate
C11355
CHEBI:35181

Overall Comment: The enzyme is composed of two parts, PabA and PabB. In the absence of PabA and glutamine, PabB will still convert ammonia and chorismate into 4-amino-4-deoxychorismate. PabA, a 21kDa subunit, converts glutamine into glutamate only in the presence of stoichiometric amounts of PabB and provides the nucleophile (ammonia) via hydrolysis of glutamine to the PabA subunit. The crystal structure used here is only of PabB, there doesn't appear to be a structure available of both components together. Of the two domains present, the Chlorismate Superfamily Fold is thought to be the site of catalysis, but the second domain, situated in the N-terminus is thought to be involved in regulating an inhibitory feedback mechanism involving tryptophan.


View similar reactions


Stepwise Description of the Reaction

Step 1Chorismate is attacked at C(2) by the nucleophilic Lys274, resulting in the conjugate elimination of water from C(4). Glu258 acts as a general acid to the departing water.
Step 2The imidazol of His168 is proposed to act as a general base towards Cys79, activating the thiol towards nucleophilic attack at the glutamine carbonyl.
Step 3The anionic tetrahedral intermediate collapses. This generates the ammonia which is subsequently transferred to the aminodeoxychorismate synthase catalytic centre in the PapB subunit through a specific channel.
Step 4Ammonia formed from the hydrolysis of glutamine attacks at the C(4) position of the chorismate-enzyme adduct, eliminating Lys274.
Step 5Glu258 acts as a general base, abstracting a proton from the C(4) amino group and regenerating the synthase catalytic site.
Step 6His168 deprotonates the water, which attacks the enzyme-glutamine complex, forming a tetrahedral intermediate.
Step 7The tetrahedral intermediate collapses, eliminating Cys79, which deprotonates His168.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Lys 274 A Side Chain
Glu 258 A Side Chain
His 168 A Side Chain
Cys 79 A Side Chain
Glu 170 A Side Chain

References

  1. J. F. Parsons et al. (2002), Biochemistry, 41, 2198-2208. Structure of Escherichia coli aminodeoxychorismate synthase: architectural conservation and diversity in chorismate-utilizing enzymes.
    Medline: 11841211
  2. K. T. Ziebart et al. (2010), Biochemistry, 49, 2851-2859. Nucleophile specificity in anthranilate synthase, aminodeoxychorismate synthase, isochorismate synthase, and salicylate synthase.
    Medline: 20170126
  3. Z. He et al. (2004), J. Am. Chem. Soc., 126, 2378-2385. Conservation of mechanism in three chorismate-utilizing enzymes.
    Medline: 14982443
  4. Z. He et al. (2006), Biochemistry, 45, 5019-5028. Direct detection and kinetic analysis of covalent intermediate formation in the 4-amino-4-deoxychorismate synthase catalyzed reaction.
    Medline: 16605270
  5. F. Massiere et al. (1998), Cell. Mol. Life Sci., 54, 205-222. The mechanism of glutamine-dependent amidotransferases.
    Medline: 9575335
  6. B. Roux et al. (1993), Biochemistry, 32, 3763-3768. p-Aminobenzoate synthesis in Escherichia coli: mutational analysis of three conserved amino acid residues of the amidotransferase PabA.
    Medline: 8096767

Homologue information for M0283 (1k0g)

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
M0314 anthranilate synthase
4.1.3.27
1qdl 3.60.120.10
0.66660.2812Compare

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

GOA logo
biosynthetic process (biological process)
folic acid-containing compound biosynthetic process (biological process)
oxo-acid-lyase activity (molecular function)
spacer
spacer