3PGH

CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2) COMPLEXED WITH A NON-SELECTIVE INHIBITOR, FLURBIPROFEN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.316 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.236 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents.

Kurumbail, R.G.Stevens, A.M.Gierse, J.K.McDonald, J.J.Stegeman, R.A.Pak, J.Y.Gildehaus, D.Miyashiro, J.M.Penning, T.D.Seibert, K.Isakson, P.C.Stallings, W.C.

(1996) Nature 384: 644-648

  • DOI: https://doi.org/10.1038/384644a0
  • Primary Citation of Related Structures:  
    1CX2, 3PGH, 4COX, 5COX, 6COX

  • PubMed Abstract: 

    Prostaglandins and glucocorticoids are potent mediators of inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibition of prostaglandin production. The pharmacological target of NSAIDs is cyclooxygenase (COX, also known as PGH synthase), which catalyses the first committed step in arachidonic-acid metabolism. Two isoforms of the membrane protein COX are known: COX-1, which is constitutively expressed in most tissues, is responsible for the physiological production of prostaglandins; and COX-2, which is induced by cytokines, mitogens and endotoxins in inflammatory cells, is responsible for the elevated production of prostaglandins during inflammation. The structure of ovine COX-1 complexed with several NSAIDs has been determined. Here we report the structures of unliganded murine COX-2 and complexes with flurbiprofen, indomethacin and SC-558, a selective COX-2 inhibitor, determined at 3.0 to 2.5 A resolution. These structures explain the structural basis for the selective inhibition of COX-2, and demonstrate some of the conformational changes associated with time-dependent inhibition.


  • Organizational Affiliation

    G.D. Searle, St Louis, Missouri 63198, USA. rgkuru@punchiri.monsanto.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CYCLOOXYGENASE-2
A, B, C, D
587Mus musculusMutation(s): 0 
EC: 1.14.99.1
UniProt
Find proteins for Q05769 (Mus musculus)
Explore Q05769 
Go to UniProtKB:  Q05769
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ05769
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HEM
Query on HEM

Download Ideal Coordinates CCD File 
H [auth A],
M [auth B],
R [auth C],
W [auth D]
PROTOPORPHYRIN IX CONTAINING FE
C34 H32 Fe N4 O4
KABFMIBPWCXCRK-RGGAHWMASA-L
FLP
Query on FLP

Download Ideal Coordinates CCD File 
I [auth A],
N [auth B],
S [auth C],
X [auth D]
FLURBIPROFEN
C15 H13 F O2
SYTBZMRGLBWNTM-JTQLQIEISA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
J [auth B]
K [auth B]
E [auth A],
F [auth A],
G [auth A],
J [auth B],
K [auth B],
L [auth B],
O [auth C],
P [auth C],
Q [auth C],
T [auth D],
U [auth D],
V [auth D]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FLP BindingDB:  3PGH Ki: min: 770, max: 5500 (nM) from 3 assay(s)
IC50: min: 10, max: 1995 (nM) from 6 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.316 
  • R-Value Work: 0.236 
  • R-Value Observed: 0.236 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 179.5α = 90
b = 133.8β = 90
c = 117.1γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MERLOTphasing
X-PLORrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1997-12-24
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Database references, Derived calculations, Structure summary
  • Version 1.4: 2023-08-09
    Changes: Database references, Refinement description, Structure summary