PDBsum entry 2o1o

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Structural genomics, unknown function PDB id
Protein chains
335 a.a. *
RIS ×2
_MG ×6
Waters ×28
* Residue conservation analysis
PDB id:
Name: Structural genomics, unknown function
Title: Cryptosporidium parvum putative polyprenyl pyrophosphate synthase (cgd4_2550) in complex with risedronate.
Structure: Putative farnesyl pyrophosphate synthase. Chain: a, b. Fragment: residues 38-384. Engineered: yes
Source: Cryptosporidium parvum. Organism_taxid: 5807. Gene: cgd4_2550. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.42Å     R-factor:   0.186     R-free:   0.213
Authors: M.Chruszcz,J.D.Artz,A.Dong,J.Dunford,J.Lew,Y.Zhao, I.Kozieradski,K.L.Kavanaugh,U.Oppermann,M.Sundstrom, J.Weigelt,A.M.Edwards,C.H.Arrowsmith,A.Bochkarev,R.Hui, W.Minor,Sgc,Structural Genomics Consortium (Sgc)
Key ref: J.D.Artz et al. (2008). Targeting a uniquely nonspecific prenyl synthase with bisphosphonates to combat cryptosporidiosis. Chem Biol, 15, 1296-1306. PubMed id: 19101474
29-Nov-06     Release date:   12-Dec-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q5CR09  (Q5CR09_CRYPI) -  Putative farnesyl pyrophosphate synthase (Fragment)
384 a.a.
335 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     isoprenoid biosynthetic process   1 term 
  Biochemical function     transferase activity     1 term  


Chem Biol 15:1296-1306 (2008)
PubMed id: 19101474  
Targeting a uniquely nonspecific prenyl synthase with bisphosphonates to combat cryptosporidiosis.
J.D.Artz, J.E.Dunford, M.J.Arrowood, A.Dong, M.Chruszcz, K.L.Kavanagh, W.Minor, R.G.Russell, F.H.Ebetino, U.Oppermann, R.Hui.
Cryptosporidiosis is a neglected disease without a wholly effective drug. We present a study demonstrating nitrogen-containing bisphosphonates (N-BPs) to be capable of inhibiting Cryptosporidium parvum at low micromolar concentrations in infected MDCK cells. Predictably, the mechanism of action is based on inhibition of biosynthesis of isoprenoids but the target enzyme is unexpectedly a distinctive C. parvum enzyme dubbed nonspecific polyprenyl pyrophosphate synthase (CpNPPPS). This enzyme produces various isoprenoid products larger than FPP and is inhibited by N-BPs at subnanomolar concentrations. It is part of an isoprenoid pathway in Cryptosporidium distinctly different from other organisms. The proposed mechanism of action is corroborated by crystal structures of the enzyme with risedronate and zoledronate bound showing how this enzyme's unique chain length determinant region enables it to accommodate larger substrates and products. These results, combined with existing data on their clinical use, demonstrate that N-BPs are very promising anticryptosporidial drug candidates.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21084289 J.D.Artz, A.K.Wernimont, J.E.Dunford, M.Schapira, A.Dong, Y.Zhao, J.Lew, R.G.Russell, F.H.Ebetino, U.Oppermann, and R.Hui (2011).
Molecular characterization of a novel geranylgeranyl pyrophosphate synthase from Plasmodium parasites.
  J Biol Chem, 286, 3315-3322.
PDB codes: 3ldw 3mav 3ph7
20810277 M.Chruszcz, M.Domagalski, T.Osinski, A.Wlodawer, and W.Minor (2010).
Unmet challenges of structural genomics.
  Curr Opin Struct Biol, 20, 587-597.  
20689422 M.M.Cabada, and A.C.White (2010).
Treatment of cryptosporidiosis: do we know what we think we know?
  Curr Opin Infect Dis, 23, 494-499.  
20139160 T.H.Chang, F.L.Hsieh, T.P.Ko, K.H.Teng, P.H.Liang, and A.H.Wang (2010).
Structure of a heterotetrameric geranyl pyrophosphate synthase from mint (Mentha piperita) reveals intersubunit regulation.
  Plant Cell, 22, 454-467.
PDB codes: 3kra 3krc 3krf 3kro 3krp
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.