Q7D8I1 (PKS18_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alpha-pyrone synthesis polyketide synthase-like Pks18
EC=2.3.1.-

Alternative name(s):
Alpha-pyrone synthesis polyketide synthase type III Pks18
Chalcone synthase-like protein
Short name=CHS-like

Gene names

Name:	pks18
Ordered Locus Names:	Rv1372, MT1417

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	393 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the biosynthesis of tri- and tetraketide alpha-pyrones. Pks18 catalyzes the extension of medium- and long-chain aliphatic acyl-CoA substrates by using malonyl-CoA as an extender molecule to synthesize polyketide products. Ref.3
Pathway	Lipid metabolism; fatty acid biosynthesis.
Subunit structure	Homodimer. Ref.4
Sequence similarities	Belongs to the chalcone/stilbene synthases family.
Biophysicochemical properties	Kinetic parameters: KM=4.2 µM for lauroyl-CoA (at 30 degrees Celsius and at pH 7.5) Ref.3 KM=5.4 µM for palmitoyl-CoA (at 30 degrees Celsius and at pH 7.5) KM=6.1 µM for arachidoyl-CoA (at 30 degrees Celsius and at pH 7.5) KM=19.2 µM for hexanoyl-CoA (at 30 degrees Celsius and at pH 7.5) KM=49.2 µM for acetyl-CoA (at 30 degrees Celsius and at pH 7.5) KM=58.4 µM for malonyl-CoA (at 30 degrees Celsius and at pH 7.5)

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Molecular function	Acyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	chalcone biosynthetic process Inferred from direct assay Ref.3. Source: MTBBASE fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	transferase activity, transferring acyl groups other than amino-acyl groups Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 393

393

Alpha-pyrone synthesis polyketide synthase-like Pks18

PRO_0000407320

Sites

Active site

175

1

Nucleophile

Binding site

221

1

Substrate; via carbonyl oxygen

Site

205

1

Important for broad specificity for aliphatic long-chain acyl-CoA starter units

Site

209

1

Important for broad specificity for aliphatic long-chain acyl-CoA starter units

Experimental info

Mutagenesis

144

1

T → F: Completely abolishes the polyketide synthase activity with lauroyl-CoA and palmitoyl-CoA. Ref.4

Mutagenesis

148

1

A → F: Can not be recovered in the soluble form. Ref.3

Mutagenesis

148

1

A → M: Can not be recovered in the soluble form. Ref.3

Mutagenesis

148

1

A → T: Can not be recovered in the soluble form. Ref.3

Mutagenesis

175

1

C → A: Loss of polyketide synthase activity. Ref.4

Mutagenesis

205

1

C → A: No significant change in polyketide synthase activity. Ref.4

Mutagenesis

205

1

C → F: Efficiently catalyzed the synthesis of the triketide pyrone of the C6 starter unit and shows weak polyketide synthase activity with the C12 starter molecule. Ref.4

Mutagenesis

209

1

A → F: Retained reasonable polyketide synthase activity with lauroyl-CoA.

Mutagenesis

275

1

C → A: No significant change in polyketide synthase activity. Ref.4

Mutagenesis

318

1

K → A: Unable to synthesize any polyketide products. Ref.3

Mutagenesis

348

1

L → S: Increase in the synthesis of the tetraketide products. Ref.3

Secondary structure

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393

Helix Strand Turn

Details...

Beta strand

32 – 35

4

Beta strand

46 – 48

3

Helix

49 – 57

9

Helix

68 – 74

7

Beta strand

79 – 82

4

Helix

92 – 95

4

Helix

102 – 125

24

Helix

132 – 134

3

Beta strand

138 – 142

5

Helix

152 – 158

7

Beta strand

167 – 171

5

Helix

177 – 181

5

Helix

185 – 191

7

Beta strand

197 – 201

5

Helix

206 – 208

3

Helix

215 – 223

9

Beta strand

229 – 233

5

Beta strand

247 – 251

5

Helix

290 – 299

10

Helix

304 – 306

3

Helix

318 – 326

9

Helix

331 – 334

4

Helix

335 – 343

9

Helix

350 – 361

12

Beta strand

364 – 370

7

Beta strand

374 – 376

3

Beta strand

382 – 384

3

Beta strand

387 – 390

4

Sequences

	Sequence		Length	Mass (Da)
	Q7D8I1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 317D24C33B9CFD42	FASTA	393	42,032
	10 20 30 40 50 60 MNVSAESGAP RRAGQRHEVG LAQLPPAPPT TVAVIEGLAT GTPRRVVNQS DAADRVAELF 70 80 90 100 110 120 LDPGQRERIP RVYQKSRITT RRMAVDPLDA KFDVFRREPA TIRDRMHLFY EHAVPLAVDV 130 140 150 160 170 180 SKRALAGLPY RAAEIGLLVL ATSTGFIAPG VDVAIVKELG LSPSISRVVV NFMGCAAAMN 190 200 210 220 230 240 ALGTATNYVR AHPAMKALVV CIELCSVNAV FADDINDVVI HSLFGDGCAA LVIGASQVQE 250 260 270 280 290 300 KLEPGKVVVR SSFSQLLDNT EDGIVLGVNH NGITCELSEN LPGYIFSGVA PVVTEMLWDN 310 320 330 340 350 360 GLQISDIDLW AIHPGGPKII EQSVRSLGIS AELAAQSWDV LARFGNMLSV SLIFVLETMV 370 380 390 QQAESAKAIS TGVAFAFGPG VTVEGMLFDI IRR

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]	"A new family of type III polyketide synthases in Mycobacterium tuberculosis." Saxena P., Yadav G., Mohanty D., Gokhale R.S. J. Biol. Chem. 278:44780-44790(2003) [PubMed: 12941968] [Abstract] Cited for: FUNCTION AS A POLYKETIDE SYNTHASE, STARTER UNIT SPECIFICITY, MUTAGENESIS OF ALA-148; LYS-318 AND LEU-348, BIOPHYSICOCHEMICAL PROPERTIES. Strain: ATCC 25618 / H37Rv.
[4]	"A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites." Sankaranarayanan R., Saxena P., Marathe U.B., Gokhale R.S., Shanmugam V.M., Rukmini R. Nat. Struct. Mol. Biol. 11:894-900(2004) [PubMed: 15286723] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF MUTANT PHE-205 IN COMPLEX WITH SUBSTRATE, MUTAGENESIS OF THR-144; CYS-175; CYS-205 AND CYS-275, STARTER UNIT SPECIFICITY, SUBUNIT. Strain: ATCC 25618 / H37Rv.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BX842576 Genomic DNA. Translation: CAE55381.1.
AE000516 Genomic DNA. Translation: AAK45681.1.

PIR

A70958.

RefSeq

NP_335867.1. NC_002755.2.
YP_177803.1. NC_000962.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TED	X-ray	2.25	A/B/C/D	1-393	[»]
1TEE	X-ray	2.90	A/B/C/D	1-393	[»]

ProteinModelPortal

Q7D8I1.

SMR

Q7D8I1. Positions 22-393.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBMYCT00000002723; EBMYCP00000002723; EBMYCG00000002721.
EBMYCT00000072342; EBMYCP00000070401; EBMYCG00000072337.

GeneID

886797.
924569.

GenomeReviews

Gene locus MT1417 in contig AE000516_GR.
Gene locus Rv1372 in contig AL123456_GR.

KEGG

mtc:MT1417.
mtu:Rv1372.

PATRIC

18124884. VBIMycTub22151_1556.

TIGR

MT1417.

Organism-specific databases

TubercuList

Rv1372.

Phylogenomic databases

GeneTree

EBGT00050000016071.

HOGENOM

HBG588210.

OMA

GFRMGLS.

PhylomeDB

Q7D8I1.

ProtClustDB

CLSK799797.

Family and domain databases

InterPro

IPR012328. Chalcone/stilbene_synth_C.
IPR001099. Chalcone/stilbene_synthase_N.
IPR011141. Polyketide_synthase_type-III.
IPR016039. Thiolase-like.
IPR016038. Thiolase-like_subgr.
[Graphical view]

Gene3D

G3DSA:3.40.47.10. Thiolase-like_subgr. 2 hits.

Pfam

PF02797. Chal_sti_synt_C. 1 hit.
PF00195. Chal_sti_synt_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000451. PKS_III. 1 hit.

SUPFAM

SSF53901. Thiolase-like. 1 hit.

ProtoNet

Search...

Entry information

Entry name

PKS18_MYCTU

Accession

Primary (citable) accession number: Q7D8I1
Secondary accession number(s): Q79FQ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 3, 2011
Last sequence update:	July 5, 2004
Last modified:	January 25, 2012
This is version 62 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program