Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 6.3.2.1 extracted from

  • Pandey, B.; Grover, S.; Goyal, S.; Kumari, A.; Singh, A.; Jamal, S.; Kaur, J.; Grover, A.
    Alanine mutation of the catalytic sites of pantothenate synthetase causes distinct conformational changes in the ATP binding region (2018), Sci. Rep., 8, 903 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.3.2.1

Protein Variants

Protein Variants Comment Organism
H44A site-directed mutagenesis, the mutant shows reduced catalytic activity compared to the wild-type enzyme Mycobacterium tuberculosis
H47A site-directed mutagenesis, the mutant shows only weak interactions between ATP and enzyme leading to reduced protein catalytic activity compared to wild-type Mycobacterium tuberculosis
K160A site-directed mutagenesis, the mutant shows only weak interactions between ATP and enzyme leading to reduced protein catalytic activity compared to wild-type Mycobacterium tuberculosis
additional information ATP is strongly bound to the catalytic core of the wild-type enzyme, limiting its movement to form a stable complex as compared to enzyme mutants Mycobacterium tuberculosis
N69A site-directed mutagenesis, mutant shows reduced catalytic activity compared to the wild-type enzyme Mycobacterium tuberculosis
Q164A site-directed mutagenesis, mutant shows reduced catalytic activity compared to the wild-type enzyme Mycobacterium tuberculosis
Q72A site-directed mutagenesis, mutant shows reduced catalytic activity compared to the wild-type enzyme Mycobacterium tuberculosis

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + (R)-pantoate + beta-alanine Mycobacterium tuberculosis
-
 AMP + diphosphate + (R)-pantothenate
-
 ?
ATP + (R)-pantoate + beta-alanine Mycobacterium tuberculosis ATCC 25618 / H37Rv
-
 AMP + diphosphate + (R)-pantothenate
-
 ?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WIL5
-
-
Mycobacterium tuberculosis ATCC 25618 / H37Rv P9WIL5
-
-

Reaction

Reaction Comment Organism Reaction ID
ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate the enzyme catalyzes the ATP-dependent condensation of pantoate with beta-alanine via a pantoyl adenylate intermediate and follows a bi uni uni bi ping pong kinetic mechanism. The Mg2+ dependent reaction involves two sequential steps. Initially binding of ATP with pantoate, leads to formation of pantoyl adenylate and release of diphosphate. Second step involves nucleophilic attack by beta-alanine on the active carbonyl group of pantoyl adenylate and subsequent release of AMP and pantothenate Mycobacterium tuberculosis
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + (R)-pantoate + beta-alanine
-
 Mycobacterium tuberculosis AMP + diphosphate + (R)-pantothenate
-
 ?
ATP + (R)-pantoate + beta-alanine
-
 Mycobacterium tuberculosis ATCC 25618 / H37Rv AMP + diphosphate + (R)-pantothenate
-
 ?

Synonyms

Synonyms Comment Organism
PanC
-
 Mycobacterium tuberculosis
Pantothenate synthetase
-
 Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
ATP ATP is strongly bound to the catalytic core of the wild-type enzyme, limiting its movement to form a stable complex, ATP-enzyme binding structure analysis, molecular mechanism, detailed overview. Molecular dynamics simulations and free energy calculations Mycobacterium tuberculosis

General Information

General Information Comment Organism
malfunction alanine mutation of the catalytic sites of pantothenate synthetase causes distinct conformational changes in the ATP binding region. Analysis of the molecular mechanism of decreased affinity of the enzyme for ATP caused by alanine mutations using molecular dynamics simulations and free energy calculations Mycobacterium tuberculosis
additional information significance and importance of conserved active site residues including His44, His47, Asn69, Gln72, Lys160 and Gln164 in substrate binding and formation of pantoyl adenylate intermediate. Molecular dynamics simulations of enzyme PS-ATP complex, substrate binding pocket and residue interactions analysis Mycobacterium tuberculosis