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PDBsum entry 1ak5
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Oxidoreductase PDB id
1ak5

 

 

 

 

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Contents
Protein chain
329 a.a. *
Ligands
SO4
Waters ×171
* Residue conservation analysis
PDB id:
1ak5
Name: Oxidoreductase
Title: Inosine monophosphate dehydrogenase (impdh) from tritrichomonas foetus
Structure: Inosine-5'-monophosphate dehydrogenase. Chain: a. Synonym: impdh. Engineered: yes. Other_details: disulfide linkage 26-459
Source: Tritrichomonas foetus. Organism_taxid: 5724. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Tetramer (from PDB file)
Resolution:
2.30Å     R-factor:   0.218     R-free:   0.265
Authors: F.G.Whitby
Key ref:
F.G.Whitby et al. (1997). Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex. Biochemistry, 36, 10666-10674. PubMed id: 9271497 DOI: 10.1021/bi9708850
Date:
28-May-97     Release date:   17-Sep-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
P50097  (IMDH_TRIFO) -  Inosine-5'-monophosphate dehydrogenase from Tritrichomonas foetus
Seq:
Struc: 		503 a.a.
329 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.205  - Imp dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		AMP and GMP Biosynthesis
      Reaction: IMP + NAD+ + H2O = XMP + NADH + H+
IMP
 + NAD(+)
 + H2O
 = XMP
 + NADH
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1021/bi9708850 Biochemistry 36:10666-10674 (1997)
PubMed id: 9271497  
 
 
Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex.
F.G.Whitby, H.Luecke, P.Kuhn, J.R.Somoza, J.A.Huete-Perez, J.D.Phillips, C.P.Hill, R.J.Fletterick, C.C.Wang.
 
  ABSTRACT  
 
Inosine-5'-monophosphate dehydrogenase (IMPDH) is an attractive drug target for the control of parasitic infections. The enzyme catalyzes the oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the committed step in de novo guanosine monophosphate (GMP) biosynthesis. We have determined the crystal structures of IMPDH from the protozoan parasite Tritrichomonas foetus in the apo form at 2.3 A resolution and the enzyme-XMP complex at 2.6 A resolution. Each monomer of this tetrameric enzyme is comprised of two domains, the largest of which includes an eight-stranded parallel beta/alpha-barrel that contains the enzyme active site at the C termini of the barrel beta-strands. A second domain, comprised of residues 102-220, is disordered in the crystal. IMPDH is expected to be active as a tetramer, since the active site cavity is formed by strands from adjacent subunits. An intrasubunit disulfide bond, seen in the crystal structure, may stabilize the protein in a less active form, as high concentrations of reducing agent have been shown to increase enzyme activity. Disorder at the active site suggests that a high degree of flexibility may be inherent in the catalytic function of IMPDH. Unlike IMPDH from other species, the T. foetus enzyme has a single arginine that is largely responsible for coordinating the substrate phosphate in the active site. This structural uniqueness may facilitate structure-based identification and design of compounds that specifically inhibit the parasite enzyme.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21035731 D.R.Gollapalli, I.S.Macpherson, G.Liechti, S.K.Gorla, J.B.Goldberg, and L.Hedstrom (2010).
Structural determinants of inhibitor selectivity in prokaryotic IMP dehydrogenases.
  Chem Biol, 17, 1084-1091.  
19480389 L.Hedstrom (2009).
IMP dehydrogenase: structure, mechanism, and inhibition.
  Chem Rev, 109, 2903-2928.  
16682407 J.Y.Ha, J.Y.Min, S.K.Lee, H.S.Kim, d.o. .J.Kim, K.H.Kim, H.H.Lee, H.K.Kim, H.J.Yoon, and S.W.Suh (2006).
Crystal structure of 2-nitropropane dioxygenase complexed with FMN and substrate. Identification of the catalytic base.
  J Biol Chem, 281, 18660-18667.
PDB codes: 2gjl 2gjn
15269207 N.N.Umejiego, C.Li, T.Riera, L.Hedstrom, and B.Striepen (2004).
Cryptosporidium parvum IMP dehydrogenase: identification of functional, structural, and dynamic properties that can be exploited for drug design.
  J Biol Chem, 279, 40320-40327.  
15206931 R.Laupitz, S.Hecht, S.Amslinger, F.Zepeck, J.Kaiser, G.Richter, N.Schramek, S.Steinbacher, R.Huber, D.Arigoni, A.Bacher, W.Eisenreich, and F.Rohdich (2004).
Biochemical characterization of Bacillus subtilis type II isopentenyl diphosphate isomerase, and phylogenetic distribution of isoprenoid biosynthesis pathways.
  Eur J Biochem, 271, 2658-2669.  
11959921 B.Striepen, M.W.White, C.Li, M.N.Guerini, S.B.Malik, J.M.Logsdon, C.Liu, and M.S.Abrahamsen (2002).
Genetic complementation in apicomplexan parasites.
  Proc Natl Acad Sci U S A, 99, 6304-6309.  
12235158 G.L.Prosise, J.Z.Wu, and H.Luecke (2002).
Crystal structure of Tritrichomonas foetus inosine monophosphate dehydrogenase in complex with the inhibitor ribavirin monophosphate reveals a catalysis-dependent ion-binding site.
  J Biol Chem, 277, 50654-50659.
PDB codes: 1me7 1me8
11875050 S.J.Bowne, L.S.Sullivan, S.H.Blanton, C.L.Cepko, S.Blackshaw, D.G.Birch, D.Hughbanks-Wheaton, J.R.Heckenlively, and S.P.Daiger (2002).
Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) cause the RP10 form of autosomal dominant retinitis pigmentosa.
  Hum Mol Genet, 11, 559-568.  
11377202 C.Breithaupt, J.Strassner, U.Breitinger, R.Huber, P.Macheroux, A.Schaller, and T.Clausen (2001).
X-ray structure of 12-oxophytodienoate reductase 1 provides structural insight into substrate binding and specificity within the family of OYE.
  Structure, 9, 419-429.
PDB codes: 1icp 1icq 1ics
10828360 B.M.Goldstein, and T.D.Colby (2000).
Conformational constraints in NAD analogs: implications for dehydrogenase binding and specificity.
  Adv Enzyme Regul, 40, 405-426.  
10758003 F.M.McMillan, M.Cahoon, A.White, L.Hedstrom, G.A.Petsko, and D.Ringe (2000).
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.
  Biochemistry, 39, 4533-4542.
PDB code: 1eep
10677226 J.A.Digits, and L.Hedstrom (2000).
Drug selectivity is determined by coupling across the NAD+ site of IMP dehydrogenase.
  Biochemistry, 39, 1771-1777.  
10933797 K.M.Kerr, J.A.Digits, N.Kuperwasser, and L.Hedstrom (2000).
Asp338 controls hydride transfer in Escherichia coli IMP dehydrogenase.
  Biochemistry, 39, 9804-9810.  
10878288 M.D.Sintchak, and E.Nimmesgern (2000).
The structure of inosine 5'-monophosphate dehydrogenase and the design of novel inhibitors.
  Immunopharmacology, 47, 163-184.  
10194364 G.D.Markham, C.L.Bock, and C.Schalk-Hihi (1999).
Acid-base catalysis in the chemical mechanism of inosine monophosphate dehydrogenase.
  Biochemistry, 38, 4433-4440.  
10029522 J.A.Digits, and L.Hedstrom (1999).
Kinetic mechanism of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase.
  Biochemistry, 38, 2295-2306.  
10563825 J.A.Digits, and L.Hedstrom (1999).
Species-specific inhibition of inosine 5'-monophosphate dehydrogenase by mycophenolic acid.
  Biochemistry, 38, 15388-15397.  
10373003 K.Pawłowski, B.Zhang, L.Rychlewski, and A.Godzik (1999).
The Helicobacter pylori genome: from sequence analysis to structural and functional predictions.
  Proteins, 36, 20-30.  
10200156 R.Zhang, G.Evans, F.J.Rotella, E.M.Westbrook, D.Beno, E.Huberman, A.Joachimiak, and F.R.Collart (1999).
Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase.
  Biochemistry, 38, 4691-4700.
PDB code: 1zfj
10097070 T.D.Colby, K.Vanderveen, M.D.Strickler, G.D.Markham, and B.M.Goldstein (1999).
Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design.
  Proc Natl Acad Sci U S A, 96, 3531-3536.
PDB code: 1b3o
9585576 C.Schalk-Hihi, Y.Z.Zhang, and G.D.Markham (1998).
The conformation of NADH bound to inosine 5'-monophosphate dehydrogenase determined by transferred nuclear Overhauser effect spectroscopy.
  Biochemistry, 37, 7608-7616.  
9341229 K.M.Kerr, and L.Hedstrom (1997).
The roles of conserved carboxylate residues in IMP dehydrogenase and identification of a transition state analog.
  Biochemistry, 36, 13365-13373.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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