P0A5Q8 (PANB_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
3-methyl-2-oxobutanoate hydroxymethyltransferase
EC=2.1.2.11

Alternative name(s):
Ketopantoate hydroxymethyltransferase
Short name=KPHMT

Gene names

Name:	panB
Ordered Locus Names:	Rv2225, MT2284
ORF Names:	MTCY427.06

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	281 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 reversible reaction in which hydroxymethyl group from 5,10-methylenetetrahydrofolate is tranferred onto alpha-ketoisovalerate to form ketopantoate. Ref.3
Catalytic activity	5,10-methylenetetrahydrofolate + 3-methyl-2-oxobutanoate + H2O = tetrahydrofolate + 2-dehydropantoate. Ref.3
Cofactor	Binds 1 magnesium ion per subunit. Can also use cobalt and zinc, and nickel and calcium to a lesser extent. Ref.3 Ref.7
Pathway	Cofactor biosynthesis; (R)-pantothenate biosynthesis; (R)-pantoate from 3-methyl-2-oxobutanoate: step 1/2. HAMAP MF_00156
Subunit structure	Homodecamer; pentamer of dimers. Ref.7
Subcellular location	Cytoplasm Potential HAMAP MF_00156.
Post-translational modification	Pupylated at an undetermined lysine residue by the prokaryotic ubiquitin-like protein Pup with the help of the ligase PafA, which leads to its degradation by the proteasome. The cross-link involves the side-chain carboxylate of the C-terminal glutamate of Pup and the side-chain amino group of a lysine in PanB. Ref.6
Miscellaneous	Was identified as a natural substrate of the M.tuberculosis proteasome. HAMAP MF_00156 Was identified as a high-confidence drug target. HAMAP MF_00156
Sequence similarities	Belongs to the PanB family.
Biophysicochemical properties	Kinetic parameters: KM=240 µM for alpha-ketoisovalerate (at 37 degrees Celsius and pH 7.5) Ref.3 KM=820 µM for 5,10-methylenetetrahydrofolate (at 37 degrees Celsius and pH 7.5) Vmax=1.6 µmol/min/mg enzyme (at 37 degrees Celsius and pH 7.5) pH dependence: Optimum pH is 7.0-7.5.
Mass spectrometry	Molecular mass is 29202 Da from positions 2 - 281. Determined by ESI. Ref.3

Ontologies

Keywords
Biological process	Pantothenate biosynthesis
Cellular component	Cytoplasm
Ligand	Magnesium Metal-binding
Molecular function	Methyltransferase Transferase
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	growth Inferred from mutant phenotype. Source: MTBBASE pantothenate biosynthetic process Inferred from direct assay Ref.3. Source: MTBBASE protein homooligomerization Inferred from physical interaction Ref.7. Source: MTBBASE
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay. Source: MTBBASE
Molecular function	3-methyl-2-oxobutanoate hydroxymethyltransferase activity Inferred from direct assay Ref.3. Source: MTBBASE magnesium ion binding Inferred from direct assay Ref.3. Source: MTBBASE methyltransferase activity Inferred from electronic annotation. Source: UniProtKB-KW
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 – 281

280

3-methyl-2-oxobutanoate hydroxymethyltransferase HAMAP MF_00156

PRO_0000184864

Regions

Region

62 – 63

2

Alpha-ketoisovalerate binding By similarity

Sites

Active site

199

1

Proton acceptor By similarity

Metal binding

62

1

Magnesium

Metal binding

101

1

Magnesium By similarity

Metal binding

133

1

Magnesium

Binding site

101

1

Alpha-ketoisovalerate By similarity

Binding site

131

1

Alpha-ketoisovalerate By similarity

Secondary structure

1

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281

Helix Strand Turn

Details...

Helix

23 – 32

10

Beta strand

36 – 40

5

Helix

44 – 51

8

Turn

52 – 54

3

Beta strand

57 – 60

4

Helix

64 – 67

4

Beta strand

72 – 76

5

Helix

79 – 81

3

Helix

83 – 92

10

Beta strand

96 – 101

6

Helix

111 – 123

13

Beta strand

128 – 135

8

Helix

136 – 138

3

Helix

139 – 148

10

Beta strand

152 – 157

6

Helix

176 – 191

16

Beta strand

194 – 200

7

Helix

203 – 212

10

Beta strand

217 – 222

6

Beta strand

226 – 231

6

Helix

233 – 236

4

Helix

254 – 270

17

Sequences

	Sequence		Length	Mass (Da)
	P0A5Q8 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: E05CDDC5B7E80932	FASTA	281	29,336
	10 20 30 40 50 60 MSEQTIYGAN TPGGSGPRTK IRTHHLQRWK ADGHKWAMLT AYDYSTARIF DEAGIPVLLV 70 80 90 100 110 120 GDSAANVVYG YDTTVPISID ELIPLVRGVV RGAPHALVVA DLPFGSYEAG PTAALAAATR 130 140 150 160 170 180 FLKDGGAHAV KLEGGERVAE QIACLTAAGI PVMAHIGFTP QSVNTLGGFR VQGRGDAAEQ 190 200 210 220 230 240 TIADAIAVAE AGAFAVVMEM VPAELATQIT GKLTIPTVGI GAGPNCDGQV LVWQDMAGFS 250 260 270 280 GAKTARFVKR YADVGGELRR AAMQYAQEVA GGVFPADEHS F

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: 9634230] [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: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Mycobacterium tuberculosis ketopantoate hydroxymethyltransferase: tetrahydrofolate-independent hydroxymethyltransferase and enolization reactions with alpha-keto acids." Sugantino M., Zheng R., Yu M., Blanchard J.S. Biochemistry 42:191-199(2003) [PubMed: 12515554] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-11, CATALYTIC ACTIVITY, FUNCTION, REACTION MECHANISM, BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, COFACTOR.
[4]	"Identification of substrates of the Mycobacterium tuberculosis proteasome." Pearce M.J., Arora P., Festa R.A., Butler-Wu S.M., Gokhale R.S., Darwin K.H. EMBO J. 25:5423-5432(2006) [PubMed: 17082771] [Abstract] Cited for: PROTEASOME SUBSTRATE. Strain: ATCC 25618 / H37Rv.
[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: 19099550] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
[6]	"Prokaryotic ubiquitin-like protein (Pup) is coupled to substrates via the side chain of its C-terminal glutamate." Sutter M., Damberger F.F., Imkamp F., Allain F.H., Weber-Ban E. J. Am. Chem. Soc. 132:5610-5612(2010) [PubMed: 20355727] [Abstract] Cited for: PUPYLATION, NATURE OF THE CROSS-LINK. Strain: ATCC 25618 / H37Rv.
[7]	"The crystal structure of the first enzyme in the pantothenate biosynthetic pathway, ketopantoate hydroxymethyltransferase, from M. tuberculosis." Chaudhuri B.N., Sawaya M.R., Kim C.-Y., Waldo G.S., Park M.S., Terwilliger T.C., Yeates T.O. Structure 11:753-764(2003) [PubMed: 12842039] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS, COFACTOR, SUBUNIT.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842579 Genomic DNA. Translation: CAA94648.1.
AE000516 Genomic DNA. Translation: AAK46569.1.

PIR

E70776.

RefSeq

NP_216741.1. NC_000962.2.
NP_336755.1. NC_002755.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OY0	X-ray	2.80	A/B/C/D/E	1-281	[»]

ProteinModelPortal

P0A5Q8.

SMR

P0A5Q8. Positions 18-279.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBMYCT00000000953; EBMYCP00000000953; EBMYCG00000000953.
EBMYCT00000070409; EBMYCP00000068468; EBMYCG00000070404.

GeneID

887440.
924142.

GenomeReviews

Gene locus MT2284 in contig AE000516_GR.
Gene locus Rv2225 in contig AL123456_GR.

KEGG

mtc:MT2284.
mtu:Rv2225.

PATRIC

18126768. VBIMycTub22151_2496.

TIGR

MT2284.

Organism-specific databases

TubercuList

Rv2225.

Phylogenomic databases

GeneTree

EBGT00050000015555.

HOGENOM

HBG299908.

OMA

MAHVGLM.

PhylomeDB

P0A5Q8.

ProtClustDB

PRK00311.

Family and domain databases

HAMAP

MF_00156. PanB.
[Tree]

InterPro

IPR003700. Pantoate_hydroxy_MeTrfase.
IPR015813. Pyrv/PenolPyrv_Kinase.
[Graphical view]

Gene3D

G3DSA:3.20.20.60. Pyrv/PenolPyrv_Kinase_cat. 1 hit.

KO

K00606.

PANTHER

PTHR20881. Pantoate_transf. 1 hit.

Pfam

PF02548. Pantoate_transf. 1 hit.
[Graphical view]

PIRSF

PIRSF000388. Pantoate_hydroxy_MeTrfase. 1 hit.

SUPFAM

SSF51621. Pyrv/PenolPyrv_Kinase_cat. 1 hit.

TIGRFAMs

TIGR00222. PanB. 1 hit.

ProtoNet

Search...

Entry information

Entry name

PANB_MYCTU

Accession

Primary (citable) accession number: P0A5Q8
Secondary accession number(s): Q10505

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	January 25, 2012
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program