3KHJ

C. parvum inosine monophosphate dehydrogenase bound by inhibitor C64


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.226 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

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.

(2010) J Am Chem Soc 132: 1230-1231

  • DOI: https://doi.org/10.1021/ja909947a
  • Primary Citation of Related Structures:  
    3FFS, 3KHJ

  • PubMed Abstract: 

    Cryptosporidium parvum is a potential biowarfare agent, an important AIDS pathogen, and a major cause of diarrhea and malnutrition. No vaccines or effective drug treatment exist to combat Cryptosporidium infection. This parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) to obtain guanine nucleotides, and inhibition of this enzyme blocks parasite proliferation. Here, we report the first crystal structures of CpIMPDH. These structures reveal the structural basis of inhibitor selectivity and suggest a strategy for further optimization. Using this information, we have synthesized low-nanomolar inhibitors that display 10(3) selectivity for the parasite enzyme over human IMPDH2.


  • Organizational Affiliation

    Departments of Biology, Brandeis University, MS009, 415 South Street, Waltham, Massachusetts 02454, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Inosine-5-monophosphate dehydrogenase
A, B, C, D, E
A, B, C, D, E, F, G, H
361Cryptosporidium parvum Iowa IIMutation(s): 0 
Gene Names: cgd6_20GuaB
EC: 1.1.1.205
UniProt
Find proteins for Q5CPK7 (Cryptosporidium parvum (strain Iowa II))
Explore Q5CPK7 
Go to UniProtKB:  Q5CPK7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ5CPK7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
C64
Query on C64

Download Ideal Coordinates CCD File 
K [auth B],
O [auth D],
T [auth H]
N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
C18 H13 Br N4 O S
GUHIASUSWSGRHY-UHFFFAOYSA-N
IMP
Query on IMP

Download Ideal Coordinates CCD File 
I [auth A]
J [auth B]
L [auth C]
M [auth D]
P [auth E]
I [auth A],
J [auth B],
L [auth C],
M [auth D],
P [auth E],
Q [auth F],
R [auth G],
S [auth H]
INOSINIC ACID
C10 H13 N4 O8 P
GRSZFWQUAKGDAV-KQYNXXCUSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
N [auth D]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
C64 PDBBind:  3KHJ IC50: 28 (nM) from 1 assay(s)
BindingDB:  3KHJ IC50: min: 27, max: 28 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.226 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 83.481α = 90
b = 166.141β = 105.14
c = 101.289γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-02-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2014-07-02
    Changes: Structure summary
  • Version 1.3: 2017-08-02
    Changes: Refinement description, Source and taxonomy
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references, Derived calculations