UniProtKB - P9WKI7 (IMDH_MYCTU)
Protein
Inosine-5'-monophosphate dehydrogenase
Gene
guaB
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Functioni
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth (PubMed:20491506, PubMed:21081761). Does not catalyze the reverse reaction, i.e. the conversion of XMP to IMP (PubMed:21081761). Appears to be essential for the optimal growth of M.tuberculosis (PubMed:12657046).UniRule annotation3 Publications
Catalytic activityi
- EC:1.1.1.205UniRule annotation2 Publications
Cofactori
K+UniRule annotation1 Publication
Activity regulationi
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH (By similarity). Inhibited by the products XMP and NADH. Significantly inhibited in vitro by a panel of diphenyl urea-based derivatives and a series of novel classes of inhibitors, which are also potent anti-mycobacterial agents against M.tuberculosis and M.smegmatis (PubMed:21081761) (PubMed:22479467). Is also inhibited by a mycophenolic adenine dinucleotide (MAD) derivative in which a 1,2,3-triazole linker was incorporated as isosteric replacement of the pyrophosphate linker, thereby mimicking NAD (PubMed:20491506). Other inhibitors with modular structures consisting of two aromatic moieties connected by different linkers (such as urea and amide) have been identified and shown to exhibit antitubercular activity (PubMed:26440283).UniRule annotation4 Publications
Kineticsi
kcat is 0.53 sec(-1).1 Publication
- KM=78 µM for inosine 5'-phosphate1 Publication
- KM=1005 µM for NAD+1 Publication
- KM=128.1 µM for inosine 5'-phosphate1 Publication
- KM=610.5 µM for NAD+1 Publication
pH dependencei
Optimum pH is 8-8.5.1 Publication
Temperature dependencei
Optimum temperature is 37 degrees Celsius.1 Publication
: XMP biosynthesis via de novo pathway Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes XMP from IMP.UniRule annotationProteins known to be involved in this subpathway in this organism are:
- Inosine-5'-monophosphate dehydrogenase (guaB)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes XMP from IMP, the pathway XMP biosynthesis via de novo pathway and in Purine metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 283 | NADUniRule annotation1 Publication | 1 | |
Binding sitei | 289 | NAD1 Publication | 1 | |
Metal bindingi | 336 | Potassium; via carbonyl oxygenUniRule annotation1 Publication | 1 | |
Metal bindingi | 338 | Potassium; via carbonyl oxygenUniRule annotation1 Publication | 1 | |
Binding sitei | 339 | IMPUniRule annotation1 Publication | 1 | |
Active sitei | 341 | Thioimidate intermediateUniRule annotation1 Publication | 1 | |
Metal bindingi | 341 | Potassium; via carbonyl oxygenUniRule annotation1 Publication | 1 | |
Binding sitei | 343 | NAD1 Publication | 1 | |
Active sitei | 443 | Proton acceptorUniRule annotation1 Publication | 1 | |
Binding sitei | 458 | IMP; via carbonyl oxygenUniRule annotation1 Publication | 1 | |
Binding sitei | 458 | NAD1 Publication | 1 | |
Metal bindingi | 511 | Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1 Publication | 1 | |
Metal bindingi | 512 | Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1 Publication | 1 | |
Metal bindingi | 513 | Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 334 – 336 | NADUniRule annotation | 3 |
GO - Molecular functioni
- IMP dehydrogenase activity Source: MTBBASE
- metal ion binding Source: UniProtKB-UniRule
- nucleotide binding Source: UniProtKB-UniRule
GO - Biological processi
- GMP biosynthetic process Source: MTBBASE
- GTP biosynthetic process Source: GO_Central
- IMP catabolic process Source: MTBBASE
- XMP biosynthetic process Source: MTBBASE
Keywordsi
Molecular function | Oxidoreductase |
Biological process | GMP biosynthesis, Purine biosynthesis |
Ligand | Metal-binding, NAD, Potassium |
Enzyme and pathway databases
BioCyci | MTBH37RV:G185E-7688-MONOMER |
UniPathwayi | UPA00601;UER00295 |
Names & Taxonomyi
Protein namesi | Recommended name: Inosine-5'-monophosphate dehydrogenaseUniRule annotation (EC:1.1.1.205UniRule annotation2 Publications)Short name: IMP dehydrogenaseUniRule annotation Short name: IMPDUniRule annotation Short name: IMPDHUniRule annotation Alternative name(s): IMPDH21 Publication |
Gene namesi | Name:guaBUniRule annotation Synonyms:guaB22 PublicationsImported Ordered Locus Names:Rv3411c ORF Names:MTCY78.17 |
Organismi | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
Taxonomic identifieri | 83332 [NCBI] |
Taxonomic lineagei | Bacteria › Actinobacteria › Corynebacteriales › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex › |
Proteomesi |
|
Organism-specific databases
TubercuListi | Rv3411c |
Subcellular locationi
GO - Cellular componenti
- cell wall Source: MTBBASE
- plasma membrane Source: MTBBASE
Pathology & Biotechi
Disruption phenotypei
Cells lacking this gene display impaired growth.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000093702 | 1 – 529 | Inosine-5'-monophosphate dehydrogenaseAdd BLAST | 529 |
Proteomic databases
PaxDbi | P9WKI7 |
PRIDEi | P9WKI7 |
Interactioni
Subunit structurei
Homotetramer.
UniRule annotation1 PublicationProtein-protein interaction databases
STRINGi | 83332.Rv3411c |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P9WKI7 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 129 – 185 | CBS 1UniRule annotationAdd BLAST | 57 | |
Domaini | 189 – 246 | CBS 2UniRule annotationAdd BLAST | 58 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 374 – 376 | IMP bindingUniRule annotation1 Publication | 3 | |
Regioni | 397 – 398 | IMP bindingUniRule annotation1 Publication | 2 | |
Regioni | 421 – 425 | IMP bindingUniRule annotation1 Publication | 5 |
Sequence similaritiesi
Belongs to the IMPDH/GMPR family.UniRule annotation
Keywords - Domaini
CBS domain, RepeatPhylogenomic databases
eggNOGi | ENOG4105CP4 Bacteria COG0516 LUCA COG0517 LUCA |
KOi | K00088 |
OMAi | SSMGYCG |
PhylomeDBi | P9WKI7 |
Family and domain databases
CDDi | cd00381 IMPDH, 1 hit |
Gene3Di | 3.20.20.70, 1 hit |
HAMAPi | MF_01964 IMPDH, 1 hit |
InterProi | View protein in InterPro IPR013785 Aldolase_TIM IPR000644 CBS_dom IPR005990 IMP_DH IPR015875 IMP_DH/GMP_Rdtase_CS IPR001093 IMP_DH_GMPRt |
Pfami | View protein in Pfam PF00571 CBS, 2 hits PF00478 IMPDH, 1 hit |
PIRSFi | PIRSF000130 IMPDH, 1 hit |
SMARTi | View protein in SMART SM00116 CBS, 2 hits |
TIGRFAMsi | TIGR01302 IMP_dehydrog, 1 hit |
PROSITEi | View protein in PROSITE PS51371 CBS, 2 hits PS00487 IMP_DH_GMP_RED, 1 hit |
i Sequence
Sequence statusi: Complete.
P9WKI7-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSRGMSGLED SSDLVVSPYV RMGGLTTDPV PTGGDDPHKV AMLGLTFDDV
60 70 80 90 100
LLLPAASDVV PATADTSSQL TKKIRLKVPL VSSAMDTVTE SRMAIAMARA
110 120 130 140 150
GGMGVLHRNL PVAEQAGQVE MVKRSEAGMV TDPVTCRPDN TLAQVDALCA
160 170 180 190 200
RFRISGLPVV DDDGALVGII TNRDMRFEVD QSKQVAEVMT KAPLITAQEG
210 220 230 240 250
VSASAALGLL RRNKIEKLPV VDGRGRLTGL ITVKDFVKTE QHPLATKDSD
260 270 280 290 300
GRLLVGAAVG VGGDAWVRAM MLVDAGVDVL VVDTAHAHNR LVLDMVGKLK
310 320 330 340 350
SEVGDRVEVV GGNVATRSAA AALVDAGADA VKVGVGPGSI CTTRVVAGVG
360 370 380 390 400
APQITAILEA VAACRPAGVP VIADGGLQYS GDIAKALAAG ASTAMLGSLL
410 420 430 440 450
AGTAEAPGEL IFVNGKQYKS YRGMGSLGAM RGRGGATSYS KDRYFADDAL
460 470 480 490 500
SEDKLVPEGI EGRVPFRGPL SSVIHQLTGG LRAAMGYTGS PTIEVLQQAQ
510 520
FVRITPAGLK ESHPHDVAMT VEAPNYYAR
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL123456 Genomic DNA Translation: CCP46233.1 |
PIRi | H70736 |
RefSeqi | NP_217928.1, NC_000962.3 WP_003900682.1, NZ_NVQJ01000027.1 |
Genome annotation databases
EnsemblBacteriai | CCP46233; CCP46233; Rv3411c |
GeneIDi | 887498 |
KEGGi | mtu:Rv3411c mtv:RVBD_3411c |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL123456 Genomic DNA Translation: CCP46233.1 |
PIRi | H70736 |
RefSeqi | NP_217928.1, NC_000962.3 WP_003900682.1, NZ_NVQJ01000027.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4ZQM | X-ray | 1.60 | A | 1-125 | [»] | |
A | 253-529 | [»] | ||||
4ZQN | X-ray | 2.00 | A | 1-125 | [»] | |
A | 253-529 | [»] | ||||
4ZQO | X-ray | 1.76 | A | 1-125 | [»] | |
A | 253-529 | [»] | ||||
4ZQP | X-ray | 1.90 | A | 1-125 | [»] | |
A | 253-529 | [»] | ||||
4ZQR | X-ray | 1.69 | A/B/C/D | 1-125 | [»] | |
A/B/C/D | 253-529 | [»] | ||||
5UPU | X-ray | 2.90 | A | 1-125 | [»] | |
A | 256-529 | [»] | ||||
5UPV | X-ray | 1.63 | A | 1-125 | [»] | |
A | 256-529 | [»] | ||||
SMRi | P9WKI7 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 83332.Rv3411c |
Proteomic databases
PaxDbi | P9WKI7 |
PRIDEi | P9WKI7 |
Genome annotation databases
EnsemblBacteriai | CCP46233; CCP46233; Rv3411c |
GeneIDi | 887498 |
KEGGi | mtu:Rv3411c mtv:RVBD_3411c |
Organism-specific databases
TubercuListi | Rv3411c |
Phylogenomic databases
eggNOGi | ENOG4105CP4 Bacteria COG0516 LUCA COG0517 LUCA |
KOi | K00088 |
OMAi | SSMGYCG |
PhylomeDBi | P9WKI7 |
Enzyme and pathway databases
UniPathwayi | UPA00601;UER00295 |
BioCyci | MTBH37RV:G185E-7688-MONOMER |
Family and domain databases
CDDi | cd00381 IMPDH, 1 hit |
Gene3Di | 3.20.20.70, 1 hit |
HAMAPi | MF_01964 IMPDH, 1 hit |
InterProi | View protein in InterPro IPR013785 Aldolase_TIM IPR000644 CBS_dom IPR005990 IMP_DH IPR015875 IMP_DH/GMP_Rdtase_CS IPR001093 IMP_DH_GMPRt |
Pfami | View protein in Pfam PF00571 CBS, 2 hits PF00478 IMPDH, 1 hit |
PIRSFi | PIRSF000130 IMPDH, 1 hit |
SMARTi | View protein in SMART SM00116 CBS, 2 hits |
TIGRFAMsi | TIGR01302 IMP_dehydrog, 1 hit |
PROSITEi | View protein in PROSITE PS51371 CBS, 2 hits PS00487 IMP_DH_GMP_RED, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IMDH_MYCTU | |
Accessioni | P9WKI7Primary (citable) accession number: P9WKI7 Secondary accession number(s): L0TCG3, P65167, Q50715 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2014 |
Last sequence update: | April 16, 2014 | |
Last modified: | September 18, 2019 | |
This is version 34 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references