Overview for MACiE Entry M0229
EC Number: 18.104.22.168 (A member of the Ligases, Forming carbon-nitrogen bonds, Acidamino-acid ligases (peptide synthases))
Enzyme Name: pantoate-beta-alanine ligase
Biological Species: Mycobacterium tuberculosis (Bacteria)
Catalytic Chain UniprotKB Accession Codes:
- P0A5R0 - Pantothenate synthetase
Representative PDB Code: 2a84 - CRYSTAL STRUCTURE OF A PANTOTHENATE SYNTHETASE COMPLEXED WITH ATP (Resolution = 1.55 Å).
Catalytic CATH Codes:
- 22.214.171.1240 - Tyrosyl-Transfer RNA Synthetase , subunit E, domain 1
- 3.30.1300.10 - Pantoate--beta-alanine Ligase; Chain: A,domain 2
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Stepwise Description of the Reaction
|Step 1||The carboxylate oxygen is involved in in-line nucleophilic attack on the alpha-phosphate of ATP to produce pyrophosphate and a pantoyl adenylate intermediate. The pyrophosphate is protonated by His147.|
|Step 2||The phosphate group of the pantoyl adenylate forms a hydrogen-bond with the amine group of the beta-alanine substrate, deprotonating it to make the beta-alanine a better nucleophile|
|Step 3||Beta-alanine initiates a nucleophilic attack on the carbonyl of the pantoyl adenylate intermediate to form a tetrahedral intermediate.|
|Step 4||The tetrahedral intermediate collapses to eliminate AMP and the product, pantothenate, which almost immediately dissociates from the active site.|
|Step 5||His47 deprotonates water in an inferred return step.|
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Catalytic Residues Involved
||Location of Function
Metal Cofactors for M0229
- S. Wang et al. (2006), Biochemistry, 45, 1554-1561. Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis, snapshots of the enzyme in action.
- R. J. Leatherbarrow et al. (1987), Biochemistry, 26, 8524-8528. Investigation of transition-state stabilization by residues histidine-45 and threonine-40 in the tyrosyl-tRNA synthetase.
- S. Wang et al. (2003), Protein Sci., 12, 1097-1108. Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate.
- R. Zheng et al. (2004), Biochemistry, 43, 7171-7178. Active site residues in Mycobacterium tuberculosis pantothenate synthetase required in the formation and stabilization of the adenylate intermediate.
- M. Saraste et al. (1990), Trends Biochem. Sci., 15, 430-434. The P-loop--a common motif in ATP- and GTP-binding proteins.
Homologue information for M0229 (2a84)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
Entries with at least one Catalytic CATH code in common (different mechanisms):
|M0279 ||phosphoadenylyl-sulfate reductase (thioredoxin) |
|M0299 ||pantetheine-phosphate adenylyltransferase |
|M0287 ||sulfate adenylyltransferase |
|M0296 ||glycerol-3-phosphate cytidylyltransferase |
|M0197 ||tyrosine-tRNA ligase |
|M0309 ||isoleucine-tRNA ligase |
|M0235 ||arginine-tRNA ligase |
|M0303 ||(carboxyethyl)arginine beta-lactam-synthase |
|M0316 ||argininosuccinate synthetase |
|M0234 ||GMP synthase (glutamine-hydrolysing) |
|M0302 ||asparagine synthase (glutamine-hydrolysing) |
View a comparison of the other reactions in MACiE with the CATH domain 126.96.36.1990
Links to this entry in other databases