P0A5R0 (PANC_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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, MT3707
ORF Names:	MTCY07H7B.20

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	309 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.3
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.3
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. HAMAP-Rule MF_00158 Was identified as a high-confidence drug target. HAMAP-Rule MF_00158
Sequence similarities	Belongs to the pantothenate synthetase family.
Biophysicochemical properties	Kinetic parameters: KM=130 µM for D-pantoate Ref.3 Ref.4 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.3

Ontologies

Keywords
Biological process	Pantothenate biosynthesis
Cellular component	Cytoplasm
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Ligase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	beta-alanine metabolic process Inferred from direct assay Ref.7. Source: MTBBASE growth Inferred from mutant phenotype PubMed 12657046. Source: MTBBASE pantothenate biosynthetic process Inferred from direct assay Ref.3. Source: MTBBASE
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from direct assay Ref.3Ref.6. Source: MTBBASE magnesium ion binding Inferred from direct assay Ref.3. Source: MTBBASE manganese ion binding Inferred from direct assay Ref.3. Source: MTBBASE pantoate-beta-alanine ligase activity Inferred from direct assay Ref.3Ref.6. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.3

Chain

2 – 309

308

Pantothenate synthetase HAMAP-Rule MF_00158

PRO_0000128245

Regions

Nucleotide binding

40 – 47

8

ATP HAMAP-Rule MF_00158

Nucleotide binding

158 – 161

4

ATP HAMAP-Rule MF_00158

Nucleotide binding

195 – 198

4

ATP HAMAP-Rule MF_00158

Sites

Active site

47

1

Proton donor

Metal binding

88

1

Magnesium

Metal binding

89

1

Magnesium; via amide nitrogen

Metal binding

92

1

Magnesium

Binding site

72

1

Beta-alanine

Binding site

72

1

Pantoate

Binding site

164

1

Pantoate

Binding site

187

1

ATP; via amide nitrogen and carbonyl oxygen

Experimental info

Mutagenesis

44

1

H → A: More than 1000-fold reduction in activity and 52-fold decrease in adenylate formation. Ref.4

Mutagenesis

47

1

H → A: More than 1000-fold reduction in activity and 60-fold decrease in adenylate formation. 10-fold decrease in the affinity for ATP. Ref.4

Mutagenesis

69

1

N → A: More than 1000-fold reduction in activity and 50-fold decrease in adenylate formation. Ref.4

Mutagenesis

72

1

Q → A: More than 1000-fold reduction in activity and 45-fold decrease in adenylate formation. Ref.4

Mutagenesis

77

1

E → G: No effect. Ref.6

Mutagenesis

160

1

K → A: More than 1000-fold reduction in activity and 50-fold decrease in the affinity for ATP. Ref.4

Mutagenesis

160

1

K → 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.4

Mutagenesis

164

1

Q → 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.4

Secondary structure

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309

Helix Strand Turn

Details...

Beta strand

12 – 14

3

Helix

17 – 29

13

Beta strand

33 – 39

7

Helix

45 – 55

11

Beta strand

60 – 66

7

Helix

70 – 72

3

Beta strand

75 – 77

3

Helix

78 – 81

4

Helix

86 – 95

10

Beta strand

100 – 102

3

Helix

106 – 109

4

Beta strand

116 – 119

4

Helix

122 – 125

4

Helix

127 – 129

3

Helix

135 – 150

16

Beta strand

153 – 158

6

Helix

159 – 161

3

Helix

162 – 174

13

Beta strand

180 – 184

5

Helix

199 – 201

3

Helix

204 – 209

6

Helix

212 – 223

12

Helix

224 – 226

3

Helix

228 – 240

13

Beta strand

246 – 254

9

Beta strand

258 – 260

3

Beta strand

264 – 274

11

Beta strand

277 – 286

10

Helix

288 – 290

3

Beta strand

294 – 296

3

Sequences

	Sequence		Length	Mass (Da)
	P0A5R0 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: EB51DBE3485F970A	FASTA	309	32,678
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"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.
[4]	"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.
[5]	"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].
[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

AE000516 Genomic DNA. Translation: AAK48065.1.
AL123456 Genomic DNA. Translation: CCP46425.1.

PIR

C70955.

RefSeq

NP_218119.1. NC_000962.3.
NP_338251.1. NC_002755.2.
YP_006517091.1. NC_018143.1.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P0A5R0.

SMR

P0A5R0. Positions 3-290.

ModBase

Search...

Protein-protein interaction databases

STRING

83332.Rv3602c.

Proteomic databases

PRIDE

P0A5R0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK48065; AAK48065; MT3707.

GeneID

13317210.
885459.
926524.

KEGG

mtc:MT3707.
mtu:Rv3602c.

PATRIC

18129903. VBIMycTub22151_4046.

Organism-specific databases

TubercuList

Rv3602c.

Phylogenomic databases

eggNOG

COG0414.

HOGENOM

HOG000175516.

KO

K01918.

OMA

EDFGSYP.

ProtClustDB

PRK00380.

Enzyme and pathway databases

SABIO-RK

P0A5R0.

UniPathway

UPA00028; UER00005.

Family and domain databases

Gene3D

3.40.50.620. 1 hit.

HAMAP

MF_00158. PanC.

InterPro

IPR003721. Pantoate_ligase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]

PANTHER

PTHR21299:SF1. PTHR21299:SF1. 1 hit.

Pfam

PF02569. Pantoate_ligase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00018. panC. 1 hit.

ProtoNet

Search...

Other

BindingDB

P0A5R0.

ChEMBL

CHEMBL6069.

EvolutionaryTrace

P0A5R0.

Entry information

Entry name

PANC_MYCTU

Accession

Primary (citable) accession number: P0A5R0
Secondary accession number(s): L0TG74, O06280

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	May 29, 2013
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program