P60472 (UPPS_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ditrans,polycis-undecaprenyl-diphosphate synthase ((2E,6E)-farnesyl-diphosphate specific)
EC=2.5.1.31

Alternative name(s):
Ditrans,polycis-undecaprenylcistransferase
Undecaprenyl diphosphate synthase
Short name=UDS
Undecaprenyl pyrophosphate synthase
Short name=UPP synthase

Gene names

Name:	ispU
Synonyms:	rth, uppS, yaeS
Ordered Locus Names:	b0174, JW0169

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

Protein attributes

Sequence length	253 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Generates ditrans,octacis-undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP) and farnesyl diphosphate (FPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide. Ref.11
Catalytic activity	(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = 8 diphosphate + di-trans,octa-cis-undecaprenyl diphosphate. HAMAP-Rule MF_01139
Cofactor	Binds 2 magnesium ions per subunit. Ref.11 Ref.12
Enzyme regulation	Inhibited by bisphophonates. Ref.14
Subunit structure	Homodimer. Ref.10 Ref.11 Ref.12 Ref.14 Ref.15
Sequence similarities	Belongs to the UPP synthase family.
Biophysicochemical properties	Kinetic parameters: KM=0.4 µM for FPP (at pH 7.5 and at 25 degrees Celsius) Ref.11 KM=4.1 µM for IPP (at pH 7.5 and at 25 degrees Celsius)
Sequence caution	The sequence AAB08603.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Cell cycle Cell division Cell shape Cell wall biogenesis/degradation Peptidoglycan synthesis
Ligand	Magnesium Metal-binding
Molecular function	Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Gram-negative-bacterium-type cell wall biogenesis Inferred from mutant phenotype Ref.6. Source: EcoCyc cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW peptidoglycan biosynthetic process Inferred from mutant phenotype Ref.6. Source: EcoCyc polyprenol biosynthetic process Inferred from direct assay PubMed 10978182. Source: EcoCyc regulation of cell shape Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay Ref.5. Source: EcoCyc
Molecular_function	di-trans,poly-cis-decaprenylcistransferase activity Inferred from direct assay PubMed 10978182. Source: EcoCyc magnesium ion binding Inferred from direct assay Ref.11. Source: EcoCyc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 253

253

Ditrans,polycis-undecaprenyl-diphosphate synthase ((2E,6E)-farnesyl-diphosphate specific) HAMAP-Rule MF_01139

PRO_0000123609

Regions

Region

26 – 30

5

Substrate binding HAMAP-Rule MF_01139

Region

71 – 73

3

Substrate binding By similarity

Region

200 – 202

3

Substrate binding HAMAP-Rule MF_01139

Sites

Active site

26

1

Active site

74

1

Proton acceptor By similarity

Metal binding

26

1

Magnesium

Metal binding

199

1

Magnesium

Metal binding

213

1

Magnesium

Binding site

31

1

Substrate Probable

Binding site

39

1

Substrate

Binding site

43

1

Substrate

Binding site

75

1

Substrate Probable

Binding site

77

1

Substrate

Binding site

194

1

Substrate

Binding site

213

1

Isopentenyl diphosphate

Site

69

1

Required for continued chain elongation

Site

137

1

Important for determining product length

Experimental info

Mutagenesis

26

1

D → A: Great decrease in activity. Ref.7

Mutagenesis

31

1

W → F: Decrease in activity; reduced affinity for decaprenyl diphosphate substrate analog. Ref.8

Mutagenesis

43

1

H → A: Great decreases the catalytic efficiency and the affinty for FPP and IPP. Ref.11

Mutagenesis

62

1

I → A: Formation predominantly of C(60) and C(65) polymers rather than the C(55) polymer. Ref.10

Mutagenesis

69

1

A → L: Produces shorter polymers. Ref.10

Mutagenesis

71

1

S → A: Decrease in activity. Ref.10

Mutagenesis

73

1

E → A: Slight decrease in activity. Ref.7 Ref.10

Mutagenesis

74

1

N → A: Decrease in activity. Ref.10

Mutagenesis

75

1

W → A or F: Decrease in activity; reduced affinity for decaprenyl diphosphate substrate analog. Ref.8 Ref.10

Mutagenesis

77

1

R → A: Decrease in activity. Ref.10

Mutagenesis

81

1

E → A: Slight decrease in activity. Ref.10

Mutagenesis

91

1

W → F: Decrease in affinity for IPP. Ref.8

Mutagenesis

103

1

H → A: No effect. Ref.10

Mutagenesis

105

1

V → A: Formation predominantly of C(60), C(65) and C(70) polymers rather than the C(55) polymer. Ref.10

Mutagenesis

137

1

L → A: Formation predominantly of a C(70) polymer rather than the C(55) polymer. Ref.10

Mutagenesis

143

1

A → V: No effect on polymer length. Ref.10

Mutagenesis

149

1

W → F: Decrease in affinity for IPP. Ref.8

Mutagenesis

150

1

D → A: Great decrease in affinity for the substrate. Ref.7

Mutagenesis

190

1

D → A: No effect. Ref.7

Mutagenesis

198

1

E → A: No effect. Ref.7

Mutagenesis

199

1

H → A: Great decreases in the catalytic efficiency and in the affinity for IPP; when associated with A-213. Ref.11

Mutagenesis

207

1

W → F: Decrease in affinity for both IPP and decaprenyl diphosphate substrate analog. Ref.8

Mutagenesis

213

1

E → A: Great decrease in activity; reduced affinity for IPP. Great decreases in the catalytic efficiency and in the affinity for IPP; when associated with A-199. Ref.7 Ref.11

Mutagenesis

218

1

D → A: Slight decrease in activity. Ref.7

Mutagenesis

221

1

W → F: Decrease in affinity for IPP. Ref.8

Mutagenesis

223

1

D → A: No effect. Ref.7

Secondary structure

1

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253

Helix Strand Turn

Details...

Helix

15 – 17

3

Beta strand

19 – 25

7

Helix

28 – 34

7

Helix

39 – 59

21

Beta strand

63 – 68

6

Helix

74 – 76

3

Helix

83 – 90

8

Helix

93 – 102

10

Beta strand

106 – 111

6

Helix

113 – 115

3

Helix

118 – 131

14

Beta strand

138 – 144

7

Helix

147 – 164

18

Helix

169 – 171

3

Helix

174 – 178

5

Turn

182 – 185

4

Beta strand

191 – 197

7

Beta strand

204 – 206

3

Helix

207 – 209

3

Beta strand

213 – 216

4

Helix

221 – 223

3

Helix

226 – 239

14

Sequences

	Sequence		Length	Mass (Da)
	P60472 [UniParc]. Last modified February 16, 2004. Version 1. Checksum: 73DC9534C14CA7B9	FASTA	253	28,444
	10 20 30 40 50 60 MMLSATQPLS EKLPAHGCRH VAIIMDGNGR WAKKQGKIRA FGHKAGAKSV RRAVSFAANN 70 80 90 100 110 120 GIEALTLYAF SSENWNRPAQ EVSALMELFV WALDSEVKSL HRHNVRLRII GDTSRFNSRL 130 140 150 160 170 180 QERIRKSEAL TAGNTGLTLN IAANYGGRWD IVQGVRQLAE KVQQGNLQPD QIDEEMLNQH 190 200 210 220 230 240 VCMHELAPVD LVIRTGGEHR ISNFLLWQIA YAELYFTDVL WPDFDEQDFE GALNAFANRE 250 RRFGGTEPGD ETA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Systematic sequencing of the Escherichia coli genome: analysis of the 4.0 - 6.0 min (189,987 - 281,416bp) region." Takemoto K., Mori H., Murayama N., Kataoka K., Yano M., Itoh T., Yamamoto Y., Inokuchi H., Miki T., Hatada E., Fukuda R., Ichihara S., Mizuno T., Makino K., Nakata A., Yura T., Sampei G., Mizobuchi K. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[2]	"Sequence of minutes 4-25 of Escherichia coli." Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., Namath A., Oefner P., Roberts D., Schramm S., Davis R.W. Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[3]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]	"Use of genomics to identify bacterial undecaprenyl pyrophosphate synthetase: cloning, expression, and characterization of the essential uppS gene." Apfel C.M., Takacs B., Fountoulakis M., Stieger M., Keck W. J. Bacteriol. 181:483-492(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[6]	"The Escherichia coli homologue of yeast RER2, a key enzyme of dolichol synthesis, is essential for carrier lipid formation in bacterial cell wall synthesis." Kato J., Fujisaki S., Nakajima K., Nishimura Y., Sato M., Nakano A. J. Bacteriol. 181:2733-2738(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[7]	"Effect of site-directed mutagenesis of the conserved aspartate and glutamate on E. coli undecaprenyl pyrophosphate synthase catalysis." Pan J.-J., Yang L.-W., Liang P.-H. Biochemistry 39:13856-13861(2000) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-26; GLU-73; ASP-150; ASP-190; GLU-198; GLU-213; ASP-218 AND ASP-223.
[8]	"Probing the conformational change of Escherichia coli undecaprenyl pyrophosphate synthase during catalysis using an inhibitor and tryptophan mutants." Chen Y.-H., Chen A.P.-C., Chen C.-T., Wang A.H.-J., Liang P.-H. J. Biol. Chem. 277:7369-7376(2002) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TRP-31; TRP-75; TRP-91; TRP-149; TRP-207 AND TRP-221.
[9]	"Mechanism of cis-prenyltransferase reaction probed by substrate analogues." Lu Y.P., Liu H.G., Teng K.H., Liang P.H. Biochem. Biophys. Res. Commun. 400:758-762(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REACTION MECHASNISM.
[10]	"Mechanism of product chain length determination and the role of a flexible loop in Escherichia coli undecaprenyl-pyrophosphate synthase catalysis." Ko T.-P., Chen Y.-K., Robinson H., Tsai P.-C., Gao Y.-G., Chen A.P.-C., Wang A.H.-J., Liang P.-H. J. Biol. Chem. 276:47474-47482(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 13-240, MUTAGENESIS OF ILE-62; ALA-69; SER-71; GLU-73; ASN-74; TRP-75; ARG-77; GLU-81; HIS-103; VAL-105; LEU-137 AND ALA-143, SUBUNIT.
[11]	"Catalytic mechanism revealed by the crystal structure of undecaprenyl pyrophosphate synthase in complex with sulfate, magnesium, and triton." Chang S.-Y., Ko T.-P., Liang P.-H., Wang A.H.-J. J. Biol. Chem. 278:29298-29307(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) OF 13-240 IN COMPLEX WITH SUBSTRATES ANALOGS AND MAGNESIUM IONS, FUNCTION AS AN UNDECAPRENYL DIPHOSPHATE SYNTHASE, MUTAGENESIS OF HIS-43; HIS-199 AND GLU-213, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, SUBUNIT.
[12]	"Substrate binding mode and reaction mechanism of undecaprenyl pyrophosphate synthase deduced from crystallographic studies." Chang S.Y., Ko T.P., Chen A.P., Wang A.H., Liang P.H. Protein Sci. 13:971-978(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH SUBSTRATE, COFACTOR, SUBUNIT.
[13]	"Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, isopentenyl pyrophosphate, and farnesyl thiopyrophosphate: roles of the metal ion and conserved residues in catalysis." Guo R.T., Ko T.P., Chen A.P., Kuo C.J., Wang A.H., Liang P.H. J. Biol. Chem. 280:20762-20774(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF WILD-TYPE AND OF MUTANT ALA-26 IN COMPLEX WITH SUBSTRATE ANALOGS AND MAGNESIUM IONS.
[14]	"Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases." Guo R.-T., Cao R., Liang P.-H., Ko T.-P., Chang T.-H., Hudock M.P., Jeng W.-Y., Chen C.K.-M., Zhang Y., Song Y., Kuo C.-J., Yin F., Oldfield E., Wang A.H.-J. Proc. Natl. Acad. Sci. U.S.A. 104:10022-10027(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS, ENZYME REGULATION, SUBUNIT.
[15]	"Applying molecular dynamics simulations to identify rarely sampled ligand-bound conformational states of undecaprenyl pyrophosphate synthase, an antibacterial target." Sinko W., de Oliveira C., Williams S., Van Wynsberghe A., Durrant J.D., Cao R., Oldfield E., McCammon J.A. Chem. Biol. Drug Des. 77:412-420(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U70214 Genomic DNA. Translation: AAB08603.1. Different initiation.
U00096 Genomic DNA. Translation: AAC73285.1.
AP009048 Genomic DNA. Translation: BAA77849.2.

PIR

F64741.

RefSeq

NP_414716.1. NC_000913.2.
YP_488476.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JP3	X-ray	1.80	A/B	1-253	[»]
1UEH	X-ray	1.73	A/B	1-253	[»]
1V7U	X-ray	2.35	A/B	1-253	[»]
1X06	X-ray	1.90	A	1-253	[»]
1X07	X-ray	2.20	A	1-253	[»]
1X08	X-ray	1.90	A	1-253	[»]
1X09	X-ray	1.87	A	1-253	[»]
2E98	X-ray	1.90	A/B	1-253	[»]
2E99	X-ray	2.00	A/B	1-253	[»]
2E9A	X-ray	2.10	A/B	1-253	[»]
2E9C	X-ray	2.05	A/B	1-253	[»]
2E9D	X-ray	2.50	A/B	1-253	[»]
3QAS	X-ray	1.70	A/B	1-253	[»]
3SGV	X-ray	1.61	A/B	1-253	[»]
3SGX	X-ray	2.45	A/B	1-253	[»]
3SH0	X-ray	1.84	A/B	1-253	[»]
3TH8	X-ray	2.11	A/B	1-253	[»]
4H2J	X-ray	1.81	A/B	1-253	[»]
4H2M	X-ray	1.78	A/B	1-253	[»]
4H2O	X-ray	2.14	A/B	1-253	[»]
4H38	X-ray	1.95	A/B	1-253	[»]
4H3A	X-ray	1.98	A/B	1-253	[»]
4H3C	X-ray	1.93	A/B	1-253	[»]

DisProt

DP00516.

ProteinModelPortal

P60472.

SMR

P60472. Positions 17-238.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48251N.

IntAct

P60472. 4 interactions.

STRING

511145.b0174.

Proteomic databases

PaxDb

P60472.

PRIDE

P60472.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC73285; AAC73285; b0174.
BAA77849; BAA77849; BAA77849.

GeneID

12931773.
944874.

KEGG

ecj:Y75_p0170.
eco:b0174.

PATRIC

32115457. VBIEscCol129921_0180.

Organism-specific databases

EchoBASE

EB3113.

EcoGene

EG13329. ispU.

Phylogenomic databases

eggNOG

COG0020.

HOGENOM

HOG000006054.

KO

K00806.

OMA

IAYSELF.

ProtClustDB

PRK10240.

Enzyme and pathway databases

BioCyc

EcoCyc:UPPSYN-MONOMER.
ECOL316407:JW0169-MONOMER.
MetaCyc:UPPSYN-MONOMER.

Gene expression databases

Genevestigator

P60472.

Family and domain databases

Gene3D

3.40.1180.10. 1 hit.

HAMAP

MF_01139. ISPT.

InterPro

IPR001441. UPP_synth-like.
IPR018520. UPP_synth-like_CS.
[Graphical view]

PANTHER

PTHR10291. PTHR10291. 1 hit.

Pfam

PF01255. Prenyltransf. 1 hit.
[Graphical view]

SUPFAM

SSF64005. UPP_synth. 1 hit.

TIGRFAMs

TIGR00055. uppS. 1 hit.

PROSITE

PS01066. UPP_SYNTHASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P60472.

Entry information

Entry name

UPPS_ECOLI

Accession

Primary (citable) accession number: P60472
Secondary accession number(s): P75668, Q47675, Q9R2E4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 16, 2004
Last sequence update:	February 16, 2004
Last modified:	May 1, 2013
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program