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P9WIL5 (PANC_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 4. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pantothenate synthetase

Short name=PS
EC=6.3.2.1
Alternative name(s):
Pantoate--beta-alanine ligase
Pantoate-activating enzyme
Gene names
Name:panC
Ordered Locus Names:Rv3602c
ORF Names:MTCY07H7B.20
OrganismMycobacterium tuberculosis (strain ATCC 25618 / H37Rv) [Reference proteome] [HAMAP]
Taxonomic identifier83332 [NCBI]
Taxonomic lineageBacteriaActinobacteriaActinobacteridaeActinomycetalesCorynebacterineaeMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex

Protein attributes

Sequence length309 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate. Ref.2

Catalytic activity

ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate. Ref.6

Enzyme regulation

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. Ref.2

Pathway

Cofactor biosynthesis; (R)-pantothenate biosynthesis; (R)-pantothenate from (R)-pantoate and beta-alanine: step 1/1. HAMAP-Rule MF_00158

Subcellular location

Cytoplasm Potential HAMAP-Rule MF_00158.

Miscellaneous

The reaction proceeds by a bi uni uni bi ping pong mechanism.

Was identified as a high-confidence drug target.

Sequence similarities

Belongs to the pantothenate synthetase family.

Biophysicochemical properties

Kinetic parameters:

KM=130 µM for D-pantoate Ref.2 Ref.3

KM=800 µM for beta-alanine

KM=2600 µM for ATP

KM=25.4 mM for 2-mercaptoethylamine

KM=36 mM for carbamate

KM=72 mM for 5-aminovalerate

KM=79 mM for methylamine

KM=84 mM for glycine

KM=93 mM for ethylamine

KM=103 mM for taurine

KM=108 mM for glycolate

KM=335 mM for gamma-aminobutyrate

KM=580 mM for gamma-amino-beta-hydroxybutyrate

Mass spectrometry

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

Ontologies

Keywords
   Biological processPantothenate biosynthesis
   Cellular componentCytoplasm
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionLigase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processpantothenate biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-HAMAP

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

pantoate-beta-alanine ligase activity

Inferred from electronic annotation. Source: UniProtKB-HAMAP

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.2 Ref.5
Chain2 – 309308Pantothenate synthetase HAMAP-Rule MF_00158
PRO_0000128245

Regions

Nucleotide binding40 – 478ATP HAMAP-Rule MF_00158
Nucleotide binding158 – 1614ATP HAMAP-Rule MF_00158
Nucleotide binding195 – 1984ATP HAMAP-Rule MF_00158

Sites

Active site471Proton donor
Metal binding881Magnesium
Metal binding891Magnesium; via amide nitrogen
Metal binding921Magnesium
Binding site721Beta-alanine
Binding site721Pantoate
Binding site1641Pantoate
Binding site1871ATP; via amide nitrogen and carbonyl oxygen

Amino acid modifications

Modified residue21N-acetylthreonine Ref.5

Experimental info

Mutagenesis441H → A: More than 1000-fold reduction in activity and 52-fold decrease in adenylate formation. Ref.3
Mutagenesis471H → A: More than 1000-fold reduction in activity and 60-fold decrease in adenylate formation. 10-fold decrease in the affinity for ATP. Ref.3
Mutagenesis691N → A: More than 1000-fold reduction in activity and 50-fold decrease in adenylate formation. Ref.3
Mutagenesis721Q → A: More than 1000-fold reduction in activity and 45-fold decrease in adenylate formation. Ref.3
Mutagenesis771E → G: No effect. Ref.6
Mutagenesis1601K → A: More than 1000-fold reduction in activity and 50-fold decrease in the affinity for ATP. Ref.3
Mutagenesis1601K → 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. Ref.3
Mutagenesis1641Q → 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. Ref.3

Secondary structure

......................................................... 309
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P9WIL5 [UniParc].

Last modified April 16, 2014. Version 1.
Checksum: EB51DBE3485F970A

FASTA30932,678
        10         20         30         40         50         60 
MTIPAFHPGE LNVYSAPGDV ADVSRALRLT GRRVMLVPTM GALHEGHLAL VRAAKRVPGS 

        70         80         90        100        110        120 
VVVVSIFVNP MQFGAGEDLD AYPRTPDDDL AQLRAEGVEI AFTPTTAAMY PDGLRTTVQP 

       130        140        150        160        170        180 
GPLAAELEGG PRPTHFAGVL TVVLKLLQIV RPDRVFFGEK DYQQLVLIRQ LVADFNLDVA 

       190        200        210        220        230        240 
VVGVPTVREA DGLAMSSRNR YLDPAQRAAA VALSAALTAA AHAATAGAQA ALDAARAVLD 

       250        260        270        280        290        300 
AAPGVAVDYL ELRDIGLGPM PLNGSGRLLV AARLGTTRLL DNIAIEIGTF AGTDRPDGYR 


AILESHWRN 

« Hide

References

« Hide 'large scale' references
[1]"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence."
Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. expand/collapse author list , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G.
Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract]
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]"Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry."
Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K., Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R., Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M., Kumar P. expand/collapse author list , Chaerkady R., Ramachandran S., Dash D., Pandey A.
Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL123456 Genomic DNA. Translation: CCP46425.1.
PIRC70955.
RefSeqNP_218119.1. NC_000962.3.
YP_006517091.1. NC_018143.2.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP9WIL5.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID885459.

Organism-specific databases

TubercuListRv3602c.

Phylogenomic databases

PhylomeDBP9WIL5.

Enzyme and pathway databases

UniPathwayUPA00028; UER00005.

Family and domain databases

Gene3D3.40.50.620. 1 hit.
HAMAPMF_00158. PanC.
InterProIPR003721. Pantoate_ligase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PfamPF02569. Pantoate_ligase. 1 hit.
[Graphical view]
TIGRFAMsTIGR00018. panC. 1 hit.
ProtoNetSearch...

Entry information

Entry namePANC_MYCTU
AccessionPrimary (citable) accession number: P9WIL5
Secondary accession number(s): L0TG74, O06280, P0A5R0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: July 9, 2014
This is version 4 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names