P96208 (PAPA5_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phthiocerol/phthiodiolone dimycocerosyl transferase
EC=2.3.1.-

Alternative name(s):
Acyltransferase PapA5
Phthiocerol/phthiodiolone O-acyltransferase
Polyketide synthase-associated protein A5

Gene names

Name:	papA5
Ordered Locus Names:	Rv2939, MT3009
ORF Names:	MTCY19H9.07

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	422 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosic acids, the final step in the phthiocerol and phthiodiolone dimycocerosate esters (PDIM) synthesis. Can directly transfer the mycocerosate bound to the mycocerosic acid synthase (mas) onto the substrate alcohols. Is also able to catalyze acyl transfer using various nucleophiles as acceptors and several acyl-CoA thioesters as donors in vitro; preference is observed for saturated medium chain alcohols and long chain acyl-CoA thioesters. Ref.3 Ref.5
Subunit structure	Monomer. Interacts directly with the acyl carrier protein (ACP) domain of the mycocerosic acid synthase (mas) protein. Interacts with FhaB. Ref.5 Ref.7 Ref.8
Domain	Consists of two structural domains that are related to each other. Ref.8
Post-translational modification	Phosphorylated by PknB. Dephosphorylated by PstP. Ref.7
Miscellaneous	Was identified as a high-confidence drug target.
Sequence similarities	Belongs to the acyltransferase PapA5 family.
Biophysicochemical properties	Kinetic parameters: KM=500 µM for 1-octanol Ref.3 Ref.5 KM=24 µM for 2-dodecanol KM=4 µM for palmitoyl-CoA KM=118 µM for lauroyl-CoA KM=0.39 µM for mycoserosate acylated to mas protein pH dependence: Optimum pH is 6.5.

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism
Molecular function	Acyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DIM/DIP cell wall layer assembly Inferred from direct assay Ref.5. Source: MTBBASE lipid biosynthetic process Inferred from direct assay Ref.5. Source: MTBBASE
Molecular_function	O-acyltransferase activity Inferred from direct assay Ref.5. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 422

422

Phthiocerol/phthiodiolone dimycocerosyl transferase

PRO_0000058229

Sites

Active site

124

1

Proton acceptor Ref.8

Site

128

1

Structural role in the organization of the active site

Site

312

1

Important for mas ACP domain recognition

Experimental info

Mutagenesis

123

1

H → A: About 2-fold decrease in activity. Ref.3

Mutagenesis

124

1

H → A: 76-fold decrease in activity. Ref.3

Mutagenesis

128

1

D → A: 65-fold decrease in activity. Ref.3

Mutagenesis

143

1

Y → F: Less than 1.9-fold decrease in activity. Ref.3

Mutagenesis

234

1

R → E: 4-fold decrease in affinity for acylated mas protein. No change in catalytic activity. Ref.5

Mutagenesis

312

1

R → E: 40-fold decrease in affinity for acylated mas protein. No change in catalytic activity. Ref.5

Secondary structure

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422

Helix Strand Turn

Details...

Beta strand

5 – 9

5

Helix

12 – 19

8

Beta strand

23 – 32

10

Helix

36 – 49

14

Helix

51 – 53

3

Beta strand

54 – 59

6

Beta strand

63 – 69

7

Beta strand

72 – 74

3

Beta strand

78 – 80

3

Turn

100 – 102

3

Beta strand

104 – 110

7

Beta strand

113 – 115

3

Beta strand

117 – 123

7

Helix

124 – 126

3

Helix

129 – 148

20

Beta strand

149 – 151

3

Helix

164 – 170

7

Turn

186 – 189

4

Beta strand

213 – 216

4

Helix

220 – 230

11

Turn

231 – 234

4

Helix

237 – 253

17

Beta strand

260 – 267

8

Turn

268 – 271

4

Beta strand

272 – 274

3

Turn

278 – 280

3

Beta strand

285 – 292

8

Helix

300 – 317

18

Helix

319 – 322

4

Helix

327 – 332

6

Beta strand

336 – 338

3

Beta strand

342 – 345

4

Beta strand

360 – 368

9

Beta strand

371 – 373

3

Beta strand

378 – 384

7

Beta strand

387 – 395

9

Helix

399 – 412

14

Turn

413 – 415

3

Sequences

	Sequence		Length	Mass (Da)
	P96208 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 19156C6B9FCC3AA7	FASTA	422	45,429
	10 20 30 40 50 60 MFPGSVIRKL SHSEEVFAQY EVFTSMTIQL RGVIDVDALS DAFDALLETH PVLASHLEQS 70 80 90 100 110 120 SDGGWNLVAD DLLHSGICVI DGTAATNGSP SGNAELRLDQ SVSLLHLQLI LREGGAELTL 130 140 150 160 170 180 YLHHCMADGH HGAVLVDELF SRYTDAVTTG DPGPITPQPT PLSMEAVLAQ RGIRKQGLSG 190 200 210 220 230 240 AERFMSVMYA YEIPATETPA VLAHPGLPQA VPVTRLWLSK QQTSDLMAFG REHRLSLNAV 250 260 270 280 290 300 VAAAILLTEW QLRNTPHVPI PYVYPVDLRF VLAPPVAPTE ATNLLGAASY LAEIGPNTDI 310 320 330 340 350 360 VDLASDIVAT LRADLANGVI QQSGLHFGTA FEGTPPGLPP LVFCTDATSF PTMRTPPGLE 370 380 390 400 410 420 IEDIKGQFYC SISVPLDLYS CAVYAGQLII EHHGHIAEPG KSLEAIRSLL CTVPSEYGWI ME

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]	"Mycobacterial polyketide-associated proteins are acyltransferases: proof of principle with Mycobacterium tuberculosis PapA5." Onwueme K.C., Ferreras J.A., Buglino J., Lima C.D., Quadri L.E.N. Proc. Natl. Acad. Sci. U.S.A. 101:4608-4613(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS AN ACYLTRANSFERASE, ROLE IN PDIM SYNTHESIS, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-123; HIS-124; ASP-128 AND TYR-143. Strain: ATCC 35801 / TMC 107 / Erdman.
[4]	Erratum Onwueme K.C., Ferreras J.A., Buglino J., Lima C.D., Quadri L.E.N. Proc. Natl. Acad. Sci. U.S.A. 101:6834-6834(2004)
[5]	"Dissecting the mechanism and assembly of a complex virulence mycobacterial lipid." Trivedi O.A., Arora P., Vats A., Ansari M.Z., Tickoo R., Sridharan V., Mohanty D., Gokhale R.S. Mol. Cell 17:631-643(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH MAS PROTEIN, MUTAGENESIS OF ARG-234 AND ARG-312. Strain: ATCC 25618 / H37Rv.
[6]	"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].
[7]	"Forkhead-associated domain-containing protein Rv0019c and polyketide-associated protein PapA5, from substrates of serine/threonine protein kinase PknB to interacting proteins of Mycobacterium tuberculosis." Gupta M., Sajid A., Arora G., Tandon V., Singh Y. J. Biol. Chem. 284:34723-34734(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FHAB, PHOSPHORYLATION, DEPHOSPHORYLATION BY PSTP.
[8]	"Crystal structure of PapA5, a phthiocerol dimycocerosyl transferase from Mycobacterium tuberculosis." Buglino J., Onwueme K.C., Ferreras J.A., Quadri L.E.N., Lima C.D. J. Biol. Chem. 279:30634-30642(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS), SUBUNIT, DOMAIN, ACTIVE SITES. Strain: ATCC 35801 / TMC 107 / Erdman.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842581 Genomic DNA. Translation: CAB06098.1.
AE000516 Genomic DNA. Translation: AAK47336.1.
AL123456 Genomic DNA. Translation: CCP45742.1.

PIR

G70984.

RefSeq

NP_217455.1. NC_000962.3.
NP_337522.1. NC_002755.2.
YP_006516393.1. NC_018143.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q9J	X-ray	2.75	A/B	1-422	[»]

ProteinModelPortal

P96208.

SMR

P96208. Positions 3-418.

ModBase

Search...

Protein-protein interaction databases

STRING

83332.Rv2939.

Proteomic databases

PRIDE

P96208.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK47336; AAK47336; MT3009.

GeneID

13317733.
887327.
925266.

KEGG

mtc:MT3009.
mtu:Rv2939.
mtv:RVBD_2939.

PATRIC

18128384. VBIMycTub22151_3291.

Organism-specific databases

TubercuList

Rv2939.

Phylogenomic databases

eggNOG

NOG10132.

HOGENOM

HOG000220992.

OMA

ESTNPVG.

ProtClustDB

PRK09294.

Family and domain databases

InterPro

IPR001242. Condensatn.
[Graphical view]

Pfam

PF00668. Condensation. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P96208.

Entry information

Entry name

PAPA5_MYCTU

Accession

Primary (citable) accession number: P96208
Secondary accession number(s): L0TE04

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 16, 2004
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program