P45568 (DXR_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
1-deoxy-D-xylulose 5-phosphate reductoisomerase
Short name=DXP reductoisomerase
EC=1.1.1.267

Alternative name(s):
1-deoxyxylulose-5-phosphate reductoisomerase
2-C-methyl-D-erythritol 4-phosphate synthase

Gene names

Name:	dxr
Synonyms:	ispC, yaeM
Ordered Locus Names:	b0173, JW0168

Organism

Escherichia coli (strain K12)

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	398 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP). HAMAP MF_00183
Catalytic activity	2-C-methyl-D-erythritol 4-phosphate + NADP+ = 1-deoxy-D-xylulose 5-phosphate + NADPH. HAMAP MF_00183
Cofactor	Divalent cation. Prefers magnesium, manganese or cobalt.
Enzyme regulation	Inhibited by fosmidomycin. HAMAP MF_00183
Pathway	Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis via DXP pathway; isopentenyl diphosphate from 1-deoxy-D-xylulose 5-phosphate: step 1/6. HAMAP MF_00183
Subunit structure	Homodimer. Ref.12 Ref.13 Ref.15
Sequence similarities	Belongs to the DXR family.
Biophysicochemical properties	Kinetic parameters: Measured in the presence of manganese ions. KM=250 µM for DXP Ref.10 pH dependence: Optimum pH is 7.0-8.5. Temperature dependence: Optimum temperature is 40-60 degrees Celsius.

Ontologies

Keywords
Biological process	Isoprene biosynthesis
Ligand	Cobalt Magnesium Manganese Metal-binding NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	isoprenoid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW ubiquinone biosynthetic process Inferred from direct assay Ref.10. Source: EcoCyc
Molecular function	1-deoxy-D-xylulose-5-phosphate reductoisomerase activity Inferred from direct assay Ref.10. Source: EcoCyc NADPH binding Inferred from electronic annotation. Source: InterPro metal ion binding 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

Chain

1 – 398

398

1-deoxy-D-xylulose 5-phosphate reductoisomerase HAMAP MF_00183

PRO_0000163651

Regions

Nucleotide binding

7 – 36

30

NADP HAMAP MF_00183

Region

222 – 228

7

Binding to substrate phosphate group HAMAP MF_00183

Sites

Metal binding

150

1

Divalent metal cation

Metal binding

152

1

Divalent metal cation

Metal binding

231

1

Divalent metal cation

Binding site

125

1

Substrate

Binding site

152

1

Substrate

Binding site

186

1

Substrate

Binding site

209

1

Substrate

Binding site

231

1

Substrate

Experimental info

Mutagenesis

14

1

G → D: Loss of solubility and activity. Ref.10

Mutagenesis

153

1

H → Q: Increase in KM for substrate. Reduces activity 35-fold. Ref.10

Mutagenesis

209

1

H → Q: Increase in KM for substrate. Reduces activity 5000-fold. Ref.10

Mutagenesis

231

1

E → K: No effect on KM for substrate. Reduces activity by over 99.9%. Ref.10

Mutagenesis

257

1

H → Q: Strong increase in KM for substrate. Loss of activity. Ref.10

Secondary structure

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398

Helix Strand Turn

Details...

Beta strand

2 – 8

7

Helix

12 – 23

12

Turn

25 – 27

3

Beta strand

28 – 37

10

Helix

39 – 49

11

Beta strand

52 – 58

7

Helix

59 – 71

13

Beta strand

77 – 81

5

Helix

82 – 89

8

Beta strand

96 – 99

4

Helix

107 – 115

9

Beta strand

119 – 122

4

Helix

126 – 142

17

Beta strand

145 – 148

4

Helix

151 – 158

8

Helix

162 – 165

4

Turn

166 – 170

5

Helix

174 – 176

3

Beta strand

178 – 185

8

Beta strand

191 – 193

3

Helix

195 – 200

6

Helix

203 – 206

4

Beta strand

210 – 212

3

Helix

216 – 223

8

Helix

226 – 238

13

Helix

243 – 245

3

Beta strand

246 – 250

5

Beta strand

256 – 262

7

Beta strand

267 – 271

5

Helix

277 – 285

9

Helix

299 – 301

3

Turn

312 – 314

3

Helix

316 – 327

12

Helix

329 – 347

19

Helix

355 – 366

12

Helix

375 – 396

22

Sequences

	Sequence		Length	Mass (Da)
	P45568 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 8B532683A4FF1207	FASTA	398	43,388
	10 20 30 40 50 60 MKQLTILGST GSIGCSTLDV VRHNPEHFRV VALVAGKNVT RMVEQCLEFS PRYAVMDDEA 70 80 90 100 110 120 SAKLLKTMLQ QQGSRTEVLS GQQAACDMAA LEDVDQVMAA IVGAAGLLPT LAAIRAGKTI 130 140 150 160 170 180 LLANKESLVT CGRLFMDAVK QSKAQLLPVD SEHNAIFQSL PQPIQHNLGY ADLEQNGVVS 190 200 210 220 230 240 ILLTGSGGPF RETPLRDLAT MTPDQACRHP NWSMGRKISV DSATMMNKGL EYIEARWLFN 250 260 270 280 290 300 ASASQMEVLI HPQSVIHSMV RYQDGSVLAQ LGEPDMRTPI AHTMAWPNRV NSGVKPLDFC 310 320 330 340 350 360 KLSALTFAAP DYDRYPCLKL AMEAFEQGQA ATTALNAANE ITVAAFLAQQ IRFTDIAALN 370 380 390 LSVLEKMDMR EPQCVDDVLS VDANAREVAR KEVMRLAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis." Takahashi S., Kuzuyama T., Watanabe H., Seto H. Proc. Natl. Acad. Sci. U.S.A. 95:9879-9884(1998) [PubMed: 9707569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[2]	"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.
[3]	"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.
[4]	"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: 9278503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[5]	"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: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], SEQUENCE REVISION TO 277-284. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]	"Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-4.1 min (110,917-193,643 bp) region." Fujita N., Mori H., Yura T., Ishihama A. Nucleic Acids Res. 22:1637-1639(1994) [PubMed: 8202364] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-204. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[7]	"Identification and characterization of the smbA gene, a suppressor of the mukB null mutant of Escherichia coli." Yamanaka K., Ogura T., Niki H., Hiraga S. J. Bacteriol. 174:7517-7526(1992) [PubMed: 1447125] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49.
[8]	"Detection of new genes in a bacterial genome using Markov models for three gene classes." Borodovsky M., McIninch J., Koonin E.V., Rudd K.E., Medigue C., Danchin A. Nucleic Acids Res. 23:3554-3562(1995) [PubMed: 7567469] [Abstract] Cited for: IDENTIFICATION.
[9]	"Biosynthesis of terpenoids: 1-deoxy-D-xylulose-5-phosphate reductoisomerase from Escherichia coli is a class B dehydrogenase." Radykewicz T., Rohdich F., Wungsintaweekul J., Herz S., Kis K., Eisenreich W., Bacher A., Zenk M.H., Arigoni D. FEBS Lett. 465:157-160(2000) [PubMed: 10631325] [Abstract] Cited for: CHARACTERIZATION.
[10]	"Characterization of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, an enzyme involved in isopentenyl diphosphate biosynthesis, and identification of its catalytic amino acid residues." Kuzuyama T., Takahashi S., Takagi M., Seto H. J. Biol. Chem. 275:19928-19932(2000) [PubMed: 10787409] [Abstract] Cited for: CHARACTERIZATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLY-14; HIS-153; HIS-209; GLU-231 AND HIS-257.
[11]	"Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase complexed with cofactors: implications of a flexible loop movement upon substrate binding." Yajima S., Nonaka T., Kuzuyama T., Seto H., Ohsawa K. J. Biochem. 131:313-317(2002) [PubMed: 11872159] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2-398 IN COMPLEX WITH NADPH.
[12]	"Crystal structure of 1-deoxy-D-xylulose-5-phosphate reductoisomerase, a crucial enzyme in the non-mevalonate pathway of isoprenoid biosynthesis." Reuter K., Sanderbrand S., Jomaa H., Wiesner J., Steinbrecher I., Beck E., Hintz M., Klebe G., Stubbs M.T. J. Biol. Chem. 277:5378-5384(2002) [PubMed: 11741911] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), SUBUNIT.
[13]	"Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC). Implications for the catalytic mechanism and anti-malaria drug development." Steinbacher S., Kaiser J., Eisenreich W., Huber R., Bacher A., Rohdich F. J. Biol. Chem. 278:18401-18407(2003) [PubMed: 12621040] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS AND FOSMIDOMYCIN, SUBUNIT.
[14]	"Crystallographic structures of two bisphosphonate:1-deoxyxylulose-5-phosphate reductoisomerase complexes." Yajima S., Hara K., Sanders J.M., Yin F., Ohsawa K., Wiesner J., Jomaa H., Oldfield E. J. Am. Chem. Soc. 126:10824-10825(2004) [PubMed: 15339150] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-398 IN COMPLEX WITH SUBSTRATE ANALOG.
[15]	"The crystal structure of E.coli 1-deoxy-D-xylulose-5-phosphate reductoisomerase in a ternary complex with the antimalarial compound fosmidomycin and NADPH reveals a tight-binding closed enzyme conformation." Mac Sweeney A., Lange R., Fernandes R.P., Schulz H., Dale G.E., Douangamath A., Proteau P.J., Oefner C. J. Mol. Biol. 345:115-127(2005) [PubMed: 15567415] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH SUBSTRATE; FOSMIDOMYCIN AND NADP, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB013300 Genomic DNA. Translation: BAA32426.1.
U70214 Genomic DNA. Translation: AAB08602.1.
U00096 Genomic DNA. Translation: AAC73284.1.
AP009048 Genomic DNA. Translation: BAA77848.2.
D13334 Genomic DNA. No translation available.

PIR

E64741.

RefSeq

NP_414715.1. NC_000913.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JVS	X-ray	2.20	A/B	2-398	[»]
1K5H	X-ray	2.50	A/B/C	1-398	[»]
1ONN	X-ray	2.60	A/B	1-398	[»]
1ONO	X-ray	2.50	A/B	1-398	[»]
1ONP	X-ray	2.50	A/B	1-398	[»]
1Q0H	X-ray	2.20	A	1-398	[»]
1Q0L	X-ray	2.65	A	1-398	[»]
1Q0Q	X-ray	1.90	A/B	1-398	[»]
1T1R	X-ray	2.30	A/B	2-398	[»]
1T1S	X-ray	2.40	A/B	2-398	[»]
2EGH	X-ray	2.20	A/B	2-398	[»]
3ANL	X-ray	2.10	A/B	2-398	[»]
3ANM	X-ray	2.00	A/B	2-398	[»]
3ANN	X-ray	2.00	A/B	2-398	[»]
3R0I	X-ray	2.10	A/B	1-398	[»]

ProteinModelPortal

P45568.

SMR

P45568. Positions 1-398.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-9484N.

IntAct

P45568. 6 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBESCT00000003838; EBESCP00000003838; EBESCG00000003135.
EBESCT00000014771; EBESCP00000014062; EBESCG00000013831.

GeneID

945019.

GenomeReviews

Gene locus JW0168 in contig AP009048_GR.
Gene locus b0173 in contig U00096_GR.

KEGG

ecj:JW0168.
eco:b0173.

PATRIC

32115455. VBIEscCol129921_0179.

Organism-specific databases

EchoBASE

EB2575.

EcoGene

EG12715. dxr.

Phylogenomic databases

eggNOG

COG0743.

GeneTree

EBGT00050000011215.

HOGENOM

HBG430762.

OMA

IHSMVEY.

PhylomeDB

P45568.

ProtClustDB

PRK05447.

Enzyme and pathway databases

BioCyc

EcoCyc:DXPREDISOM-MONOMER.
MetaCyc:DXPREDISOM-MONOMER.

Gene expression databases

Genevestigator

P45568.

Family and domain databases

HAMAP

MF_00183. DXP_reductoisom.
[Tree]

InterPro

IPR003821. DXP_reductoisomerase.
IPR013644. DXP_reductoisomerase_C.
IPR013512. DXP_reductoisomerase_N.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

KO

K00099.

Pfam

PF08436. DXP_redisom_C. 1 hit.
PF02670. DXP_reductoisom. 1 hit.
[Graphical view]

PIRSF

PIRSF006205. Dxp_reductismrs. 1 hit.

TIGRFAMs

TIGR00243. Dxr. 1 hit.

ProtoNet

Search...

Entry information

Entry name

DXR_ECOLI

Accession

Primary (citable) accession number: P45568
Secondary accession number(s): P77209, Q8KMY5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program