1DYR

THE STRUCTURE OF PNEUMOCYSTIS CARINII DIHYDROFOLATE REDUCTASE TO 1.9 ANGSTROMS RESOLUTION


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The structure of Pneumocystis carinii dihydrofolate reductase to 1.9 A resolution.

Champness, J.N.Achari, A.Ballantine, S.P.Bryant, P.K.Delves, C.J.Stammers, D.K.

(1994) Structure 2: 915-924

  • DOI: https://doi.org/10.1016/s0969-2126(94)00093-x
  • Primary Citation of Related Structures:  
    1DYR

  • PubMed Abstract: 

    The fungal pathogen Pneumocystis carinii causes a pneumonia which is an opportunistic infection of AIDS patients. Current therapy includes the dihydrofolate reductase (DHFR) inhibitor trimethoprim which is selective but only a relatively weak inhibitor of the enzyme for P. carinii. Determination of the three-dimensional structure of the enzyme should form the basis for design of more potent and selective therapeutic agents for treatment of the disease. The structure of P. carinii DHFR in complex with reduced nicotinamide adenine dinucleotide phosphate and trimethoprim has accordingly been solved by X-ray crystallography. The structure of the ternary complex has been refined at 1.86 A resolution (R = 0.181). A similar ternary complex with piritrexim (which is a tighter binding, but less selective inhibitor) has also been solved, as has the binary complex holoenzyme, both at 2.5 A resolution. These structures show how two drugs interact with a fungal DHFR. A comparison of the three-dimensional structure of this relatively large DHFR with bacterial or mammalian enzyme-inhibitor complexes determined previously highlights some additional secondary structure elements in this particular enzyme species. These comparisons provide further insight into the principles governing DHFR-inhibitor interaction, in which the volume of the active site appears to determine the strength of inhibitor binding.


  • Organizational Affiliation

    Physical Sciences Department, Wellcome Research Laboratories, Beckenham, Kent, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DIHYDROFOLATE REDUCTASE206Pneumocystis cariniiMutation(s): 0 
Gene Names: C-DNA P.CARINII DHFR
EC: 1.5.1.3
UniProt
Find proteins for P16184 (Pneumocystis carinii)
Explore P16184 
Go to UniProtKB:  P16184
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16184
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NDP
Query on NDP

Download Ideal Coordinates CCD File 
B [auth A]NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H30 N7 O17 P3
ACFIXJIJDZMPPO-NNYOXOHSSA-N
TOP
Query on TOP

Download Ideal Coordinates CCD File 
C [auth A]TRIMETHOPRIM
C14 H18 N4 O3
IEDVJHCEMCRBQM-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
TOP BindingDB:  1DYR Ki: min: 151.36, max: 2.80e+5 (nM) from 3 assay(s)
IC50: min: 1.20e+4, max: 4.30e+4 (nM) from 6 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.86 Å
  • R-Value Observed: 0.181 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.9α = 90
b = 43.6β = 117.7
c = 37.6γ = 90
Software Package:
Software NamePurpose
PROFFTrefinement
XENGENdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1995-10-15
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-07
    Changes: Data collection, Database references, Derived calculations, Other, Structure summary