Q5JGC2 · PANE_THEKO
- Protein2-dehydropantoate 2-reductase
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids309 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the NAD(P)H-dependent reduction of ketopantoate into pantoic acid. Prefers NADH rather than NADPH as the electron donor.
Catalytic activity
- (R)-pantoate + NAD+ = 2-dehydropantoate + H+ + NADHThis reaction proceeds in the backward direction.
Activity regulation
Regulated by feedback inhibition by coenzyme A (CoA). CoA acts by competing with NAD(P)H (PubMed:23941541, PubMed:26757028).
A disulfide bond is formed between CoA and Cys-84, which indicates an irreversible inhibition upon binding of CoA (PubMed:26757028).
A disulfide bond is formed between CoA and Cys-84, which indicates an irreversible inhibition upon binding of CoA (PubMed:26757028).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
6.03 μM | ketopantoate | |||||
3.01 μM | NADH | |||||
1.35 μM | NADPH | |||||
130 μM | D-pantoate | |||||
2040 μM | L-pantoate | |||||
40.9 μM | NAD+ |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
40.7 μmol/min/mg | toward ketopantoate (in the presence of NADH) | ||||
34.7 μmol/min/mg | toward NADH | ||||
3.92 μmol/min/mg | toward NADPH |
kcat is 23.1 sec-1 toward ketopantoate (in the presence of NADH). kcat is 19.7 sec-1 toward NADH. kcat is 2.22 sec-1 toward NADPH.
pH Dependence
Optimum pH is 6.4.
Temperature Dependence
Optimum temperature is 90 degrees Celsius. Is extremely thermostable.
Pathway
Cofactor biosynthesis; coenzyme A biosynthesis.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 7-12 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: GAGSIG | ||||||
Binding site | 8-10 | CoA (UniProtKB | ChEBI); inhibitor | ||||
Sequence: AGS | ||||||
Binding site | 31 | CoA (UniProtKB | ChEBI); inhibitor | ||||
Sequence: R | ||||||
Binding site | 31 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 74 | CoA (UniProtKB | ChEBI); inhibitor | ||||
Sequence: K | ||||||
Binding site | 74 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 84 | CoA (UniProtKB | ChEBI); inhibitor | ||||
Sequence: C | ||||||
Binding site | 100 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 124 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Active site | 180 | Proton donor | ||||
Sequence: K | ||||||
Binding site | 180 | substrate | ||||
Sequence: K | ||||||
Binding site | 184 | substrate | ||||
Sequence: N | ||||||
Binding site | 188 | substrate | ||||
Sequence: N | ||||||
Binding site | 198 | substrate | ||||
Sequence: N | ||||||
Binding site | 247-250 | substrate | ||||
Sequence: NYNS | ||||||
Binding site | 257 | CoA (UniProtKB | ChEBI); inhibitor | ||||
Sequence: R | ||||||
Binding site | 262 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Molecular Function | 2-dehydropantoate 2-reductase activity | |
Molecular Function | nucleotide binding | |
Biological Process | coenzyme A biosynthetic process | |
Biological Process | pantothenate biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name2-dehydropantoate 2-reductase
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageArchaea > Euryarchaeota > Thermococci > Thermococcales > Thermococcaceae > Thermococcus
Accessions
- Primary accessionQ5JGC2
Proteomes
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Disruption of the gene results in a strain with growth defects that are complemented by addition of pantoate.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 60 | Decreases efficiency of the inhibition by CoA. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 84 | Decreases efficiency of the inhibition by CoA. Inhibition shows no time-dependency. | ||||
Sequence: C → A | ||||||
Mutagenesis | 129 | Decreases efficiency of the inhibition by CoA. | ||||
Sequence: W → A |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000448239 | 1-309 | 2-dehydropantoate 2-reductase | |||
Sequence: MRIYVLGAGSIGSLFGALLARAGNDVTLIGRREQVDAINKNGLHVFGAEEFTVKPKATIYAPEEPPDLLILAVKSYSTKTALECARQCIGRNTWVLSIQNGLGNEELALKYTPNVMGGVTTNGAMLVEWGKVLWAGKGITVIGRYPTGRDDFVDEVASVFNEAGIDTSVTENAIGWKWAKAIVNSVINGLGTVLEVKNGHLKDDPHLEGISVDIAREGCMVAQQLGIEFEIHPLELLWDTIERTRENYNSTLQDIWRGRETEVDYIHGKIVEYARSVGMEAPRNELLWVLVKAKERINRGKTRNISEGC |
Interaction
Structure
Family & Domains
Domain
Cooperative binding of CoA and ketopantoate induces a closed inhibited state by interacting with the N-terminal and C-terminal domains, and seems to facilitate the disulfide bond formation.
Sequence similarities
Belongs to the ketopantoate reductase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length309
- Mass (Da)34,050
- Last updated2005-02-15 v1
- Checksum265F1F3C5C4A96FD
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AP006878 EMBL· GenBank· DDBJ | BAD86157.1 EMBL· GenBank· DDBJ | Genomic DNA |