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Overview for MACiE Entry M0229

Version history

General Information

EC Number: 6.3.2.1 (A member of the Ligases, Forming carbon-nitrogen bonds, Acid—amino-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:

  • 3.40.50.620 - Tyrosyl-Transfer RNA Synthetase , subunit E, domain 1
  • 3.30.1300.10 - Pantoate--beta-alanine Ligase; Chain: A,domain 2

Display structure information

Overall Reaction:

Image of beta-Alanine

Image of ATP

Image of (R)-Pantoate

right arrow

Image of Pantothenate

Image of AMP

Image of diphosphate

beta-Alanine
C00099
CHEBI:57966
ATP
C00002
CHEBI:30616
(R)-Pantoate
C00522
CHEBI:15980
Pantothenate
C00864
CHEBI:29032
AMP
C00020
CHEBI:456215
diphosphate
C00013
CHEBI:33019

View similar reactions


Stepwise Description of the Reaction

Step 1The 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 2The 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 3Beta-alanine initiates a nucleophilic attack on the carbonyl of the pantoyl adenylate intermediate to form a tetrahedral intermediate.
Step 4The tetrahedral intermediate collapses to eliminate AMP and the product, pantothenate, which almost immediately dissociates from the active site.
Step 5His47 deprotonates water in an inferred return step.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
His 44 A Side Chain
His 47 A Side Chain
Ser 196 A Side Chain
Ser 197 A Side Chain
Arg 198 A Side Chain

Metal Cofactors for M0229

Type Het group Number Chain
magnesium MG 1001 _ Overview

References

  1. S. Wang et al. (2006), Biochemistry, 45, 1554-1561. Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis, snapshots of the enzyme in action.
    Medline: 16460002
  2. 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.
    Medline: 3126804
  3. 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.
    Medline: 12717031
  4. 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.
    Medline: 15170354
  5. M. Saraste et al. (1990), Trends Biochem. Sci., 15, 430-434. The P-loop--a common motif in ATP- and GTP-binding proteins.
    Medline: 2126155

Homologue information for M0229 (2a84)

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
M0279 phosphoadenylyl-sulfate reductase (thioredoxin)
1.8.4.8
1sur 3.40.50.620
0.04540Compare
M0299 pantetheine-phosphate adenylyltransferase
2.7.7.3
1b6t 3.40.50.620
0.1250.5889Compare
M0287 sulfate adenylyltransferase
2.7.7.4
1g8f 3.40.50.620
0.47050.2999Compare
M0296 glycerol-3-phosphate cytidylyltransferase
2.7.7.39
1n1d 3.40.50.620
0.1250.0159Compare
M0197 tyrosine-tRNA ligase
6.1.1.1
2ts1 3.40.50.620
0.3750.2103Compare
M0309 isoleucine-tRNA ligase
6.1.1.5
1ile 3.40.50.620
0.50.0138Compare
M0235 arginine-tRNA ligase
6.1.1.19
1f7u 3.40.50.620
0.57890.3892Compare
M0303 (carboxyethyl)arginine beta-lactam-synthase
6.3.3.4
1mb9 3.40.50.620
0.47820.0167Compare
M0316 argininosuccinate synthetase
6.3.4.5
1j21 3.40.50.620
0.57890.3589Compare
M0234 GMP synthase (glutamine-hydrolysing)
6.3.5.2
1gpm 3.40.50.620
0.48710.1458Compare
M0302 asparagine synthase (glutamine-hydrolysing)
6.3.5.4
1ct9 3.40.50.620
0.42850.0642Compare

View a comparison of the other reactions in MACiE with the CATH domain 3.40.50.620


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
nucleotide binding (molecular function)
magnesium ion binding (molecular function)
pantoate-beta-alanine ligase activity (molecular function)
ATP binding (molecular function)
cytoplasm (cellular component)
pantothenate biosynthetic process (biological process)
ligase activity (molecular function)
beta-alanine metabolic process (biological process)
manganese ion binding (molecular function)
growth (biological process)
protein homodimerization activity (molecular function)
metal ion binding (molecular function)
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