P49058 (IMDH_BORBU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inosine-5'-monophosphate dehydrogenase
Short name=IMP dehydrogenase
Short name=IMPD
Short name=IMPDH
EC=1.1.1.205

Gene names

Name:	guaB
Ordered Locus Names:	BB_B17

Encoded on

Plasmid cp26 (circular 26 kb)

Organism

Borrelia burgdorferi (strain ATCC 35210 / B31 / CIP 102532 / DSM 4680) [Reference proteome] [HAMAP]

Taxonomic identifier

224326 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Spirochaetes › Spirochaetia › Spirochaetales › Spirochaetaceae › Borrelia › Borrelia burgdorferi group › Borrelia burgdorferi

Protein attributes

Sequence length	404 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 conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Essential for mouse infection by tick bite and critical for the survival in environments that appear to lack sufficient amounts of guanine, guanosine, and/or deoxyguanosine to support spirochete growth, such as mammalian host tissues. Ref.3 Ref.4
Catalytic activity	Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH. HAMAP-Rule MF_01964
Cofactor	Potassium By similarity. HAMAP-Rule MF_01964
Enzyme regulation	Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH By similarity. HAMAP-Rule MF_01964
Pathway	Purine metabolism; XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1. HAMAP-Rule MF_01964
Subunit structure	Homotetramer. Ref.3
Sequence similarities	Belongs to the IMPDH/GMPR family.
Biophysicochemical properties	Kinetic parameters: KM=29 µM for Inosine 5'-phosphate Ref.3 KM=1100 µM for NAD+

Ontologies

Keywords
Biological process	GMP biosynthesis Purine biosynthesis
Ligand	Metal-binding NAD Potassium
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Plasmid Reference proteome
Gene Ontology (GO)
Biological_process	GMP biosynthetic process Inferred from electronic annotation. Source: UniProtKB-HAMAP
Molecular_function	IMP dehydrogenase activity Inferred from electronic annotation. Source: UniProtKB-HAMAP metal ion binding Inferred from electronic annotation. Source: UniProtKB-HAMAP nucleotide binding Inferred from electronic annotation. Source: UniProtKB-HAMAP
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 – 404

403

Inosine-5'-monophosphate dehydrogenase HAMAP-Rule MF_01964

PRO_0000093692

Regions

Nucleotide binding

222 – 224

3

NAD By similarity

Region

262 – 264

3

IMP binding By similarity

Region

285 – 286

2

IMP binding By similarity

Region

309 – 313

5

IMP binding By similarity

Sites

Active site

229

1

Thioimidate intermediate By similarity

Metal binding

224

1

Potassium; via carbonyl oxygen By similarity

Metal binding

226

1

Potassium; via carbonyl oxygen By similarity

Metal binding

229

1

Potassium; via carbonyl oxygen By similarity

Metal binding

394

1

Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity

Metal binding

395

1

Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity

Metal binding

396

1

Potassium; via carbonyl oxygen; shared with tetrameric partner By similarity

Binding site

172

1

NAD By similarity

Binding site

227

1

IMP By similarity

Binding site

340

1

IMP By similarity

Secondary structure

1

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404

Helix Strand Turn

Details...

Helix

12 – 14

3

Beta strand

15 – 17

3

Helix

26 – 28

3

Beta strand

33 – 38

6

Beta strand

40 – 47

8

Turn

51 – 53

3

Helix

56 – 65

10

Beta strand

67 – 71

5

Beta strand

73 – 75

3

Helix

77 – 88

12

Beta strand

145 – 148

4

Helix

154 – 163

10

Beta strand

167 – 171

5

Helix

179 – 191

13

Beta strand

196 – 202

7

Helix

205 – 212

8

Turn

213 – 215

3

Beta strand

217 – 221

5

Helix

230 – 235

6

Helix

241 – 252

12

Beta strand

258 – 263

6

Helix

268 – 277

10

Beta strand

280 – 284

5

Helix

286 – 289

4

Beta strand

294 – 296

3

Beta strand

298 – 301

4

Beta strand

304 – 307

4

Helix

352 – 370

19

Helix

375 – 380

6

Beta strand

384 – 386

3

Sequences

	Sequence		Length	Mass (Da)
	P49058 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: A91D6D6C5CE522F1	FASTA	404	43,768
	10 20 30 40 50 60 MPNKITKEAL TFDDVSLIPR KSSVLPSEVS LKTQLTKNIS LNIPFLSSAM DTVTESQMAI 70 80 90 100 110 120 AIAKEGGIGI IHKNMSIEAQ RKEIEKVKTY KFQKTINTNG DTNEQKPEIF TAKQHLEKSD 130 140 150 160 170 180 AYKNAEHKED FPNACKDLNN KLRVGAAVSI DIDTIERVEE LVKAHVDILV IDSAHGHSTR 190 200 210 220 230 240 IIELIKKIKT KYPNLDLIAG NIVTKEAALD LISVGADCLK VGIGPGSICT TRIVAGVGVP 250 260 270 280 290 300 QITAICDVYE ACNNTNICII ADGGIRFSGD VVKAIAAGAD SVMIGNLFAG TKESPSEEII 310 320 330 340 350 360 YNGKKFKSYV GMGSISAMKR GSKSRYFQLE NNEPKKLVPE GIEGMVPYSG KLKDILTQLK 370 380 390 400 GGLMSGMGYL GAATISDLKI NSKFVKISHS SLKESHPHDV FSIT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Plasmid location of Borrelia purine biosynthesis gene homologs." Margolis N., Hogan D., Tilly K., Rosa P. J. Bacteriol. 176:6427-6432(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 35210 / B31 / CIP 102532 / DSM 4680.
[2]	"Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi." Fraser C.M., Casjens S., Huang W.M., Sutton G.G., Clayton R.A., Lathigra R., White O., Ketchum K.A., Dodson R.J., Hickey E.K., Gwinn M.L., Dougherty B.A., Tomb J.-F., Fleischmann R.D., Richardson D.L., Peterson J.D., Kerlavage A.R., Quackenbush J. , Salzberg S.L., Hanson M., van Vugt R., Palmer N., Adams M.D., Gocayne J.D., Weidman J.F., Utterback T.R., Watthey L., McDonald L.A., Artiach P., Bowman C., Garland S.A., Fujii C., Cotton M.D., Horst K., Roberts K.M., Hatch B., Smith H.O., Venter J.C. Nature 390:580-586(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 35210 / B31 / CIP 102532 / DSM 4680.
[3]	"Expression, purification, and characterization of inosine 5'-monophosphate dehydrogenase from Borrelia burgdorferi." Zhou X., Cahoon M., Rosa P., Hedstrom L. J. Biol. Chem. 272:21977-21981(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-7, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT. Strain: ATCC 35210 / B31 / CIP 102532 / DSM 4680.
[4]	"GuaA and GuaB are essential for Borrelia burgdorferi survival in the tick-mouse infection cycle." Jewett M.W., Lawrence K.A., Bestor A., Byram R., Gherardini F., Rosa P.A. J. Bacteriol. 191:6231-6241(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. Strain: ATCC 35210 / B31 / CIP 102532 / DSM 4680.
[5]	"Crystal structure at 2.4-A resolution of Borrelia burgdorferi inosine 5'-monophosphate dehydrogenase: evidence of a substrate-induced hinged-lid motion by loop 6." McMillan F.M., Cahoon M., White A., Hedstrom L., Petsko G.A., Ringe D. Biochemistry 39:4533-4542(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U13372 Genomic DNA. Translation: AAA53247.1.
AE000792 Genomic DNA. Translation: AAC66314.1.

PIR

E70218.

RefSeq

NP_047003.1. NC_001903.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EEP	X-ray	2.40	A/B	1-404	[»]

ProteinModelPortal

P49058.

SMR

P49058. Positions 3-389.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

STRING

224326.BBB17.

Chemistry

BindingDB

P49058.

Proteomic databases

PRIDE

P49058.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC66314; AAC66314; BB_B17.

GeneID

1194400.

KEGG

bbu:BB_B17.

PATRIC

20559101. VBIBorBur75917_1605.

Phylogenomic databases

eggNOG

COG0517.

KO

K00088.

OMA

SSMGYCG.

OrthoDB

EOG6GTZPV.

ProtClustDB

PRK06843.

Enzyme and pathway databases

BioCyc

BBUR224326:G9SO-1498-MONOMER.

UniPathway

UPA00601; UER00295.

Family and domain databases

Gene3D

3.20.20.70. 2 hits.

HAMAP

MF_01964. IMPDH.

InterPro

IPR013785. Aldolase_TIM.
IPR005990. IMP_DH.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]

PANTHER

PTHR11911:SF6. PTHR11911:SF6. 1 hit.

Pfam

PF00478. IMPDH. 1 hit.
[Graphical view]

PROSITE

PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P49058.

Entry information

Entry name

IMDH_BORBU

Accession

Primary (citable) accession number: P49058

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	February 19, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program