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P9WIL5

- PANC_MYCTU

UniProt

P9WIL5 - PANC_MYCTU

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Protein

Pantothenate synthetase

Gene

panC

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.1 Publication

Catalytic activityi

ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate.1 Publication

Enzyme regulationi

Pantothenate exhibits uncompetitive inhibition toward both D-pantoate and ATP, and non-competitive inhibition toward beta-alanine. AMPCPP exhibits competitive inhibition toward ATP, uncompetitive inhibition toward beta-alanine, and non-competitive inhibition toward D-pantoate. The enzyme is most active in the presence of magnesium or manganese. Other divalent cations (cobalt, nickel, zinc) are less effective.1 Publication

Kineticsi

  1. KM=130 µM for D-pantoate2 Publications
  2. KM=800 µM for beta-alanine2 Publications
  3. KM=2600 µM for ATP2 Publications
  4. KM=25.4 mM for 2-mercaptoethylamine2 Publications
  5. KM=36 mM for carbamate2 Publications
  6. KM=72 mM for 5-aminovalerate2 Publications
  7. KM=79 mM for methylamine2 Publications
  8. KM=84 mM for glycine2 Publications
  9. KM=93 mM for ethylamine2 Publications
  10. KM=103 mM for taurine2 Publications
  11. KM=108 mM for glycolate2 Publications
  12. KM=335 mM for gamma-aminobutyrate2 Publications
  13. KM=580 mM for gamma-amino-beta-hydroxybutyrate2 Publications

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei47 – 471Proton donor
Binding sitei72 – 721Beta-alanine
Binding sitei72 – 721Pantoate
Metal bindingi88 – 881Magnesium
Metal bindingi89 – 891Magnesium; via amide nitrogen
Metal bindingi92 – 921Magnesium
Binding sitei164 – 1641Pantoate
Binding sitei187 – 1871ATP; via amide nitrogen and carbonyl oxygen1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi40 – 478ATP1 Publication
Nucleotide bindingi158 – 1614ATP1 Publication
Nucleotide bindingi195 – 1984ATP1 Publication

GO - Molecular functioni

  1. ATP binding Source: MTBBASE
  2. magnesium ion binding Source: MTBBASE
  3. manganese ion binding Source: MTBBASE
  4. pantoate-beta-alanine ligase activity Source: MTBBASE
  5. protein homodimerization activity Source: MTBBASE

GO - Biological processi

  1. beta-alanine metabolic process Source: MTBBASE
  2. growth Source: MTBBASE
  3. pantothenate biosynthetic process Source: MTBBASE
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Pantothenate biosynthesis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

UniPathwayiUPA00028; UER00005.

Names & Taxonomyi

Protein namesi
Recommended name:
Pantothenate synthetase (EC:6.3.2.1)
Short name:
PS
Alternative name(s):
Pantoate--beta-alanine ligase
Pantoate-activating enzyme
Gene namesi
Name:panC
Ordered Locus Names:Rv3602c
ORF Names:MTCY07H7B.20
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaActinobacteridaeActinomycetalesCorynebacterineaeMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
ProteomesiUP000001584: Chromosome

Organism-specific databases

TubercuListiRv3602c.

Subcellular locationi

Cytoplasm Curated

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-HAMAP
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi44 – 441H → A: More than 1000-fold reduction in activity and 52-fold decrease in adenylate formation. 1 Publication
Mutagenesisi47 – 471H → A: More than 1000-fold reduction in activity and 60-fold decrease in adenylate formation. 10-fold decrease in the affinity for ATP. 1 Publication
Mutagenesisi69 – 691N → A: More than 1000-fold reduction in activity and 50-fold decrease in adenylate formation. 1 Publication
Mutagenesisi72 – 721Q → A: More than 1000-fold reduction in activity and 45-fold decrease in adenylate formation. 1 Publication
Mutagenesisi77 – 771E → G: No effect. 1 Publication
Mutagenesisi160 – 1601K → A: More than 1000-fold reduction in activity and 50-fold decrease in the affinity for ATP. 1 Publication
Mutagenesisi160 – 1601K → C: More than 1000-fold reduction in activity and 120-fold decrease in adenylate formation. The enzymatic activity and the affinity for beta-alanine can be increased 10- and 3-fold, respectively, by alkylation of cysteine of mutant C-160. 1 Publication
Mutagenesisi164 – 1641Q → A: 50-fold reduction in activity and slight reduction in the affinity for beta-alanine. 30- and 40-fold decrease in adenylate formation and pantothenate formation, respectively. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 309308Pantothenate synthetasePRO_0000128245Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylthreonine1 Publication

Keywords - PTMi

Acetylation

Structurei

Secondary structure

1
309
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi12 – 143Combined sources
Helixi17 – 2913Combined sources
Beta strandi33 – 397Combined sources
Helixi45 – 5511Combined sources
Beta strandi60 – 667Combined sources
Helixi70 – 723Combined sources
Beta strandi75 – 773Combined sources
Helixi78 – 814Combined sources
Helixi86 – 9510Combined sources
Beta strandi100 – 1023Combined sources
Helixi106 – 1094Combined sources
Beta strandi116 – 1194Combined sources
Helixi122 – 1254Combined sources
Helixi127 – 1293Combined sources
Helixi135 – 15016Combined sources
Beta strandi153 – 1586Combined sources
Helixi159 – 1613Combined sources
Helixi162 – 17413Combined sources
Beta strandi180 – 1845Combined sources
Helixi199 – 2013Combined sources
Helixi204 – 2096Combined sources
Helixi212 – 22312Combined sources
Helixi224 – 2263Combined sources
Helixi228 – 24013Combined sources
Beta strandi246 – 2549Combined sources
Beta strandi258 – 2603Combined sources
Beta strandi264 – 27411Combined sources
Beta strandi277 – 28610Combined sources
Helixi288 – 2903Combined sources
Beta strandi294 – 2963Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1MOPX-ray1.60A/B3-300[»]
1N2BX-ray1.70A/B3-300[»]
1N2EX-ray1.60A/B3-300[»]
1N2GX-ray1.80A/B3-300[»]
1N2HX-ray2.00A/B3-300[»]
1N2IX-ray1.70A/B3-300[»]
1N2JX-ray1.80A/B3-300[»]
1N2OX-ray2.10A/B3-300[»]
2A7XX-ray1.70A3-300[»]
2A84X-ray1.55A3-300[»]
2A86X-ray1.85A/B3-300[»]
2A88X-ray1.70A3-300[»]
3COVX-ray1.50A/B3-300[»]
3COWX-ray1.80A/B3-300[»]
3COYX-ray2.03A/B3-300[»]
3COZX-ray2.00A/B3-300[»]
3IMCX-ray1.60A/B3-300[»]
3IMEX-ray2.39A/B3-300[»]
3IMGX-ray1.80A/B3-300[»]
3IOBX-ray1.80A/B3-300[»]
3IOCX-ray2.50A/B3-300[»]
3IODX-ray1.75A/B3-300[»]
3IOEX-ray1.95A/B3-300[»]
3ISJX-ray2.20A/B3-300[»]
3IUBX-ray1.50A/B3-301[»]
3IUEX-ray1.73A/B3-301[»]
3IVCX-ray2.13A/B3-301[»]
3IVGX-ray1.95A/B3-301[»]
3IVXX-ray1.73A/B3-301[»]
3LE8X-ray1.70A/B3-300[»]
4DDHX-ray2.07A/B3-301[»]
4DDKX-ray1.75A/B3-301[»]
4DDMX-ray1.83A/B3-301[»]
4DE5X-ray2.25A/B3-301[»]
4EF6X-ray1.94A/B3-300[»]
4EFKX-ray1.70A/B3-300[»]
4FZJX-ray1.63A/B3-301[»]
4G5FX-ray2.33A/B3-309[»]
4G5YX-ray1.80A/B3-300[»]
ProteinModelPortaliP9WIL5.
SMRiP9WIL5. Positions 3-290.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the pantothenate synthetase family.Curated

Phylogenomic databases

KOiK01918.
PhylomeDBiP9WIL5.

Family and domain databases

Gene3Di3.40.50.620. 1 hit.
HAMAPiMF_00158. PanC.
InterProiIPR003721. Pantoate_ligase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PfamiPF02569. Pantoate_ligase. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00018. panC. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P9WIL5-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MTIPAFHPGE LNVYSAPGDV ADVSRALRLT GRRVMLVPTM GALHEGHLAL
60 70 80 90 100
VRAAKRVPGS VVVVSIFVNP MQFGAGEDLD AYPRTPDDDL AQLRAEGVEI
110 120 130 140 150
AFTPTTAAMY PDGLRTTVQP GPLAAELEGG PRPTHFAGVL TVVLKLLQIV
160 170 180 190 200
RPDRVFFGEK DYQQLVLIRQ LVADFNLDVA VVGVPTVREA DGLAMSSRNR
210 220 230 240 250
YLDPAQRAAA VALSAALTAA AHAATAGAQA ALDAARAVLD AAPGVAVDYL
260 270 280 290 300
ELRDIGLGPM PLNGSGRLLV AARLGTTRLL DNIAIEIGTF AGTDRPDGYR

AILESHWRN
Length:309
Mass (Da):32,678
Last modified:April 16, 2014 - v1
Checksum:iEB51DBE3485F970A
GO

Mass spectrometryi

Molecular mass is 32545 Da from positions 2 - 309. Determined by ESI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP46425.1.
PIRiC70955.
RefSeqiNP_218119.1. NC_000962.3.
YP_006517091.1. NC_018143.2.

Genome annotation databases

GeneIDi13317210.
885459.
KEGGimtu:Rv3602c.
mtv:RVBD_3602c.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP46425.1 .
PIRi C70955.
RefSeqi NP_218119.1. NC_000962.3.
YP_006517091.1. NC_018143.2.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1MOP X-ray 1.60 A/B 3-300 [» ]
1N2B X-ray 1.70 A/B 3-300 [» ]
1N2E X-ray 1.60 A/B 3-300 [» ]
1N2G X-ray 1.80 A/B 3-300 [» ]
1N2H X-ray 2.00 A/B 3-300 [» ]
1N2I X-ray 1.70 A/B 3-300 [» ]
1N2J X-ray 1.80 A/B 3-300 [» ]
1N2O X-ray 2.10 A/B 3-300 [» ]
2A7X X-ray 1.70 A 3-300 [» ]
2A84 X-ray 1.55 A 3-300 [» ]
2A86 X-ray 1.85 A/B 3-300 [» ]
2A88 X-ray 1.70 A 3-300 [» ]
3COV X-ray 1.50 A/B 3-300 [» ]
3COW X-ray 1.80 A/B 3-300 [» ]
3COY X-ray 2.03 A/B 3-300 [» ]
3COZ X-ray 2.00 A/B 3-300 [» ]
3IMC X-ray 1.60 A/B 3-300 [» ]
3IME X-ray 2.39 A/B 3-300 [» ]
3IMG X-ray 1.80 A/B 3-300 [» ]
3IOB X-ray 1.80 A/B 3-300 [» ]
3IOC X-ray 2.50 A/B 3-300 [» ]
3IOD X-ray 1.75 A/B 3-300 [» ]
3IOE X-ray 1.95 A/B 3-300 [» ]
3ISJ X-ray 2.20 A/B 3-300 [» ]
3IUB X-ray 1.50 A/B 3-301 [» ]
3IUE X-ray 1.73 A/B 3-301 [» ]
3IVC X-ray 2.13 A/B 3-301 [» ]
3IVG X-ray 1.95 A/B 3-301 [» ]
3IVX X-ray 1.73 A/B 3-301 [» ]
3LE8 X-ray 1.70 A/B 3-300 [» ]
4DDH X-ray 2.07 A/B 3-301 [» ]
4DDK X-ray 1.75 A/B 3-301 [» ]
4DDM X-ray 1.83 A/B 3-301 [» ]
4DE5 X-ray 2.25 A/B 3-301 [» ]
4EF6 X-ray 1.94 A/B 3-300 [» ]
4EFK X-ray 1.70 A/B 3-300 [» ]
4FZJ X-ray 1.63 A/B 3-301 [» ]
4G5F X-ray 2.33 A/B 3-309 [» ]
4G5Y X-ray 1.80 A/B 3-300 [» ]
ProteinModelPortali P9WIL5.
SMRi P9WIL5. Positions 3-290.
ModBasei Search...
MobiDBi Search...

Chemistry

ChEMBLi CHEMBL6069.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 13317210.
885459.
KEGGi mtu:Rv3602c.
mtv:RVBD_3602c.

Organism-specific databases

TubercuListi Rv3602c.

Phylogenomic databases

KOi K01918.
PhylomeDBi P9WIL5.

Enzyme and pathway databases

UniPathwayi UPA00028 ; UER00005 .

Family and domain databases

Gene3Di 3.40.50.620. 1 hit.
HAMAPi MF_00158. PanC.
InterProi IPR003721. Pantoate_ligase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view ]
Pfami PF02569. Pantoate_ligase. 1 hit.
[Graphical view ]
TIGRFAMsi TIGR00018. panC. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: ATCC 25618 / H37Rv.
  2. "Steady-state and pre-steady-state kinetic analysis of Mycobacterium tuberculosis pantothenate synthetase."
    Zheng R., Blanchard J.S.
    Biochemistry 40:12904-12912(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-11, FUNCTION, MASS SPECTROMETRY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, REACTION MECHANISM, SUBUNIT.
  3. "Active site residues in Mycobacterium tuberculosis pantothenate synthetase required in the formation and stabilization of the adenylate intermediate."
    Zheng R., Dam T.K., Brewer C.F., Blanchard J.S.
    Biochemistry 43:7171-7178(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HIS-44; HIS-47; ASN-69; GLN-72; LYS-160 AND GLN-164, BIOPHYSICOCHEMICAL PROPERTIES.
  4. "targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis."
    Raman K., Yeturu K., Chandra N.
    BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
  5. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    Strain: ATCC 25618 / H37Rv.
  6. "Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate."
    Wang S., Eisenberg D.
    Protein Sci. 12:1097-1108(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-300 OF MUTANT GLY-77 IN COMPLEX WITH SUBSTRATES; ATP ANALOG AND MAGNESIUM ION, MUTAGENESIS OF GLU-77, CATALYTIC ACTIVITY, CATALYTIC MECHANISM, SUBUNIT.
  7. "Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis, snapshots of the enzyme in action."
    Wang S., Eisenberg D.
    Biochemistry 45:1554-1561(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH SUBSTRATE; MAGNESIUM ION AND ATP, CATALYTIC MECHANISM, SUBUNIT.

Entry informationi

Entry nameiPANC_MYCTU
AccessioniPrimary (citable) accession number: P9WIL5
Secondary accession number(s): L0TG74, O06280, P0A5R0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: November 26, 2014
This is version 8 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

The reaction proceeds by a bi uni uni bi ping pong mechanism.
Was identified as a high-confidence drug target.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3