Q8T6T2 (IMDH_CRYPV) 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

ORF Names:

56k.02, cgd6_20

Organism

Cryptosporidium parvum

Taxonomic identifier

5807 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Alveolata › Apicomplexa › Conoidasida › Coccidia › Eucoccidiorida › Eimeriorina › Cryptosporidiidae › Cryptosporidium

Protein attributes

Sequence length	400 AA.
Sequence status	Complete.
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 By similarity. Ref.4
Catalytic activity	Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH. HAMAP-Rule MF_03156
Cofactor	Potassium By similarity. HAMAP-Rule MF_03156
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. Resistant to mycophenolic acid (MPA) inhibition. Ref.4
Pathway	Purine metabolism; XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1. HAMAP-Rule MF_03156
Subunit structure	Homotetramer By similarity. Ref.4
Subcellular location	Cytoplasm By similarity HAMAP-Rule MF_03156.
Miscellaneous	Cryptosporidium IMPDH was acquired through lateral transfer from eubacteria, and predictably the sensitivity to MPA differs from that of mammalian IMPDH forms. This divergence of parasite and host enzymes is exploited to design more potent parasite-specific inhibitors. HAMAP-Rule MF_03156
Sequence similarities	Belongs to the IMPDH/GMPR family.
Biophysicochemical properties	Kinetic parameters: KM=29 µM for Inosine 5'-phosphate Ref.4 KM=150 µM for NAD+

Ontologies

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 400

400

Inosine-5'-monophosphate dehydrogenase HAMAP-Rule MF_03156

PRO_0000415682

Regions

Nucleotide binding

212 – 214

3

NAD By similarity

Region

252 – 254

3

IMP binding By similarity

Region

275 – 276

2

IMP binding By similarity

Region

299 – 303

5

IMP binding By similarity

Sites

Active site

219

1

Thioimidate intermediate By similarity

Metal binding

214

1

Potassium; via carbonyl oxygen By similarity

Metal binding

216

1

Potassium; via carbonyl oxygen By similarity

Metal binding

219

1

Potassium; via carbonyl oxygen By similarity

Metal binding

383

1

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

Metal binding

384

1

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

Metal binding

385

1

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

Binding site

163

1

NAD By similarity

Binding site

217

1

IMP By similarity

Binding site

329

1

IMP By similarity

Secondary structure

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400

Helix Strand Turn

Details...

Beta strand

5 – 9

5

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

57 – 63

7

Turn

64 – 66

3

Beta strand

68 – 71

4

Beta strand

73 – 75

3

Helix

77 – 88

12

Beta strand

133 – 135

3

Beta strand

138 – 141

4

Helix

147 – 155

9

Beta strand

158 – 162

5

Helix

170 – 180

11

Beta strand

186 – 192

7

Helix

195 – 203

9

Beta strand

207 – 211

5

Helix

231 – 242

12

Beta strand

249 – 253

5

Helix

258 – 265

8

Turn

266 – 268

3

Beta strand

270 – 274

5

Helix

276 – 278

3

Beta strand

288 – 297

10

Helix

341 – 358

18

Helix

364 – 370

7

Beta strand

373 – 375

3

Sequences

	Sequence		Length	Mass (Da)
	Q8T6T2 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: DAAF96B44050DD18	FASTA	400	43,081
	10 20 30 40 50 60 MGTKNIGKGL TFEDILLVPN YSEVLPREVS LETKLTKNVS LKIPLISSAM DTVTEHLMAV 70 80 90 100 110 120 GMARLGGIGI IHKNMDMESQ VNEVLKVKNW ISNLEKNEST PDQNLDKEST DGKDTKSNNN 130 140 150 160 170 180 IDAYSNENLD NKGRLRVGAA IGVNEIERAK LLVEAGVDVI VLDSAHGHSL NIIRTLKEIK 190 200 210 220 230 240 SKMNIDVIVG NVVTEEATKE LIENGADGIK VGIGPGSICT TRIVAGVGVP QITAIEKCSS 250 260 270 280 290 300 VASKFGIPII ADGGIRYSGD IGKALAVGAS SVMIGSILAG TEESPGEKEL IGDTVYKYYR 310 320 330 340 350 360 GMGSVGAMKS GSGDRYFQEK RPENKMVPEG IEGRVKYKGE MEGVVYQLVG GLRSCMGYLG 370 380 390 400 SASIEELWKK SSYVEITTSG LRESHVHDVE IVKEVMNYSK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genetic complementation in apicomplexan parasites." Striepen B., White M.W., Li C., Guerini M.N., Malik S.B., Logsdon J.M. Jr., Liu C., Abrahamsen M.S. Proc. Natl. Acad. Sci. U.S.A. 99:6304-6309(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Iowa.
[2]	"Integrated mapping, chromosomal sequencing and sequence analysis of Cryptosporidium parvum." Bankier A.T., Spriggs H.F., Fartmann B., Konfortov B.A., Madera M., Vogel C., Teichmann S.A., Ivens A., Dear P.H. Genome Res. 13:1787-1799(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Iowa.
[3]	"Construction and analysis of full-length cDNA library of Cryptosporidium parvum." Yamagishi J., Wakaguri H., Sugano S., Kawano S., Fujisaki K., Sugimoto C., Watanabe J., Suzuki Y., Kimata I., Xuan X. Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: HNJ-1.
[4]	"Cryptosporidium parvum IMP dehydrogenase: identification of functional, structural, and dynamic properties that can be exploited for drug design." Umejiego N.N., Li C., Riera T., Hedstrom L., Striepen B. J. Biol. Chem. 279:40320-40327(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-11, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ENZYME REGULATION.
[5]	"The structural basis of Cryptosporidium-specific IMP dehydrogenase inhibitor selectivity." Macpherson I.S., Kirubakaran S., Gorla S.K., Riera T.V., D'Aquino J.A., Zhang M., Cuny G.D., Hedstrom L. J. Am. Chem. Soc. 132:1230-1231(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.19 ANGSTROMS).

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF426177 Genomic DNA. Translation: AAL83208.1.
BX538350 Genomic DNA. Translation: CAD98604.1.
FX115298 mRNA. Translation: BAJ77401.1.
FX115945 mRNA. Translation: BAJ78048.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3FFS	X-ray	3.19	A/B/C/D	1-400	[»]
4IXH	X-ray	2.10	A/B/C/D	1-400	[»]

ProteinModelPortal

Q8T6T2.

SMR

Q8T6T2. Positions 7-377.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Enzyme and pathway databases

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

BindingDB

Q8T6T2.

ChEMBL

CHEMBL6145.

EvolutionaryTrace

Q8T6T2.

Entry information

Entry name

IMDH_CRYPV

Accession

Primary (citable) accession number: Q8T6T2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 22, 2012
Last sequence update:	June 1, 2002
Last modified:	May 29, 2013
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)