P50097 (IMDH_TRIFO) 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:

IMPDH

Organism

Tritrichomonas foetus (Trichomonas foetus) (Tritrichomonas suis)

Taxonomic identifier

56690 [NCBI]

Taxonomic lineage

Eukaryota › Parabasalia › Tritrichomonadida › Tritrichomonadidae › Tritrichomonas

Protein attributes

Sequence length	503 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Rate limiting enzyme in the de novo synthesis of guanine nucleotides and therefore is involved in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism.
Catalytic activity	Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH.
Pathway	Purine metabolism; XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1.
Subunit structure	Homotetramer.
Miscellaneous	Contains 2 potassium ions bound at each subunit interface.
Sequence similarities	Belongs to the IMPDH/GMPR family. Contains 2 CBS domains.

Ontologies

Keywords
Biological process	GMP biosynthesis Purine biosynthesis
Domain	CBS domain Repeat
Ligand	DNA-binding Metal-binding NAD Potassium RNA-binding
Molecular function	Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	GMP biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW IMP dehydrogenase activity Inferred from electronic annotation. Source: EC RNA binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 503

503

Inosine-5'-monophosphate dehydrogenase

PRO_0000093676

Regions

Domain

103 – 163

61

CBS 1

Domain

167 – 228

62

CBS 2

Nucleotide binding

241 – 263

23

NAD

Sites

Active site

319

1

Thioimidate intermediate Ref.7 Ref.8

Metal binding

314

1

Potassium; via carbonyl oxygen

Metal binding

316

1

Potassium; via carbonyl oxygen

Binding site

358

1

IMP

Binding site

405

1

IMP

Secondary structure

1

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503

Helix Strand Turn

Details...

Helix

12 – 14

3

Beta strand

15 – 18

4

Helix

28 – 30

3

Beta strand

49 – 56

8

Turn

60 – 62

3

Helix

65 – 72

8

Turn

73 – 75

3

Beta strand

77 – 80

4

Helix

86 – 97

12

Beta strand

235 – 238

4

Beta strand

240 – 242

3

Helix

243 – 253

11

Beta strand

256 – 260

5

Helix

268 – 281

14

Helix

282 – 284

3

Beta strand

287 – 292

6

Helix

295 – 304

10

Beta strand

307 – 311

5

Helix

331 – 349

19

Beta strand

350 – 352

3

Beta strand

355 – 359

5

Helix

364 – 372

9

Beta strand

376 – 381

6

Helix

382 – 385

4

Beta strand

390 – 392

3

Beta strand

394 – 397

4

Beta strand

400 – 406

7

Beta strand

434 – 438

5

Helix

443 – 460

18

Helix

466 – 472

7

Beta strand

474 – 478

5

Helix

480 – 482

3

Sequences

	Sequence		Length	Mass (Da)
	P50097 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: E204EADE7ECC4134	FASTA	503	55,473
	10 20 30 40 50 60 MAKYYNEPCH TFNEYLLIPG LSTVDCIPSN VNLSTPLVKF QKGQQSEINL KIPLVSAIMQ 70 80 90 100 110 120 SVSGEKMAIA LAREGGISFI FGSQSIESQA AMVHAVKNFK AGFVVSDSNV KPDQTFADVL 130 140 150 160 170 180 AISQRTTHNT VAVTDDGTPH GVLLGLVTQR DYPIDLTQTE TKVSDMMTPF SKLVTAHQDT 190 200 210 220 230 240 KLSEANKIIW EKKLNALPII DDDQHLRYIV FRKDYDRSQV CHNELVDSQK RYLVGAGINT 250 260 270 280 290 300 RDFRERVPAL VEAGADVLCI DSSDGFSEWQ KITIGWIREK YGDKVKVGAG NIVDGEGFRY 310 320 330 340 350 360 LADAGADFIK IGIGGGSICI TREQKGIGRG QATAVIDVVA ERNKYFEETG IYIPVCSDGG 370 380 390 400 410 420 IVYDYHMTLA LAMGADFIML GRYFARFEES PTRKVTINGS VMKEYWGEGS SRARNWQRYD 430 440 450 460 470 480 LGGKQKLSFE EGVDSYVPYA GKLKDNVEAS LNKVKSTMCN CGALTIPQLQ SKAKITLVSS 490 500 VSIVEGGAHD VIVKDRINDY HPK

References

[1]	"Cloning, sequencing, and structural analysis of the DNA encoding inosine monophosphate dehydrogenase (EC 1.1.1.205) from Tritrichomonas foetus." Beck J.T., Zhao S., Wang C.C. Exp. Parasitol. 78:101-112(1994) [PubMed: 7905423] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: UNK.
[2]	Wang C.C. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Identification of the IMP binding site in the IMP dehydrogenase from Tritrichomonas foetus." Huete-Perez J.A., Wu J.C., Whitby F.G., Wang C.C. Biochemistry 34:13889-13894(1995) [PubMed: 7577983] [Abstract] Cited for: CHARACTERIZATION.
[4]	"Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo." McLean J.E., Hamaguchi N., Belenky P., Mortimer S.E., Stanton M., Hedstrom L. Biochem. J. 379:243-251(2004) [PubMed: 14766016] [Abstract] Cited for: NUCLEIC ACID-BINDING.
[5]	"Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex." Whitby F.G., Luecke H., Kuhn P., Somoza J.R., Huete-Perez J.A., Phillips J.D., Hill C.P., Fletterick R.J., Wang C.C. Biochemistry 36:10666-10674(1997) [PubMed: 9271497] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[6]	"Crystal structure of a ternary complex of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase: NAD+ orients the active site loop for catalysis." Gan L., Petsko G.A., Hedstrom L. Biochemistry 41:13309-13317(2002) [PubMed: 12403633] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 4-377 IN COMPLEX WITH SUBSTRATE AND INHIBITOR, POTASSIUM-BINDING.
[7]	"Crystal structure of Tritrichomonas foetus inosine monophosphate dehydrogenase in complex with the inhibitor ribavirin monophosphate reveals a catalysis-dependent ion-binding site." Prosise G.L., Wu J.Z., Luecke H. J. Biol. Chem. 277:50654-50659(2002) [PubMed: 12235158] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH INHIBITOR, ACTIVE SITE.
[8]	"The immunosuppressive agent mizoribine monophosphate forms a transition state analogue complex with inosine monophosphate dehydrogenase." Gan L., Seyedsayamdost M.R., Shuto S., Matsuda A., Petsko G.A., Hedstrom L. Biochemistry 42:857-863(2003) [PubMed: 12549902] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 4-377 IN COMPLEX WITH INHIBITOR (MIZORIBINE MONOPHOSPHATE) AND POTASSIUM, ACTIVE SITE.
[9]	"Crystal structures of Tritrichomonasfoetus inosine monophosphate dehydrogenase in complex with substrate, cofactor and analogs: a structural basis for the random-in ordered-out kinetic mechanism." Prosise G.L., Luecke H. J. Mol. Biol. 326:517-527(2003) [PubMed: 12559919] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-483 IN COMPLEX WITH SUBSTRATE; PRODUCT; INHIBITOR (MYCOPHENOLIC ACID; MPA) AND NAD(+).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L18917 Genomic DNA. Translation: AAB01581.1.

PIR

A58910.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AK5	X-ray	2.30	A	1-503	[»]
1LRT	X-ray	2.20	A/B/C/D	2-503	[»]
1ME7	X-ray	2.15	A	1-503	[»]
1ME8	X-ray	1.90	A	1-503	[»]
1ME9	X-ray	2.20	A	1-503	[»]
1MEH	X-ray	1.95	A	1-503	[»]
1MEI	X-ray	2.20	A	1-503	[»]
1MEW	X-ray	2.15	A	1-503	[»]
1PVN	X-ray	2.00	A/B/C/D	2-503	[»]

ProteinModelPortal

P50097.

SMR

P50097. Positions 2-494.

DisProt

DP00399.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR013785. Aldolase_TIM.
IPR000644. Cysta_beta_synth_core.
IPR018529. IMP_DH-rel.
IPR015875. IMP_DH/GMP_Rdtase_CS.
IPR001093. IMP_DH_GMPRt.
[Graphical view]

Gene3D

G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.

PANTHER

PTHR11911:SF6. IMP_DH_GMPRtase. 1 hit.

Pfam

PF00571. CBS. 2 hits.
PF00478. IMPDH. 1 hit.
[Graphical view]

PIRSF

PIRSF000130. IMPDH. 1 hit.

SMART

SM00116. CBS. 2 hits.
[Graphical view]

PROSITE

PS51371. CBS. 2 hits.
PS00487. IMP_DH_GMP_RED. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01024. Mycophenolic acid.

Entry information

Entry name

IMDH_TRIFO

Accession

Primary (citable) accession number: P50097

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	October 19, 2011
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)