3N8W

Crystal Structure of R120Q/Native Cyclooxygenase-1 Heterodimer mutant in complex with Flurbiprofen


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Comparison of Cyclooxygenase-1 Crystal Structures: Cross-Talk between Monomers Comprising Cyclooxygenase-1 Homodimers

Sidhu, R.S.Lee, J.Y.Yuan, C.Smith, W.L.

(2010) Biochemistry 49: 7069-7079

  • DOI: https://doi.org/10.1021/bi1003298
  • Primary Citation of Related Structures:  
    3N8V, 3N8W, 3N8X, 3N8Y, 3N8Z

  • PubMed Abstract: 

    Prostaglandin endoperoxide H synthases (PGHSs)-1 and -2 (also called cyclooxygenases (COXs)-1 and -2) catalyze the committed step in prostaglandin biosynthesis. Both isoforms are targets of nonsteroidal antiinflammatory drugs (NSAIDs). PGHSs are homodimers that exhibit half-of-sites COX activity; moreover, some NSAIDs cause enzyme inhibition by binding only one monomer. To learn more about the cross-talk that must be occurring between the monomers comprising each PGHS-1 dimer, we analyzed structures of PGHS-1 crystallized under five different conditions including in the absence of any tightly binding ligand and in the presence of nonspecific NSAIDs and of a COX-2 inhibitor. When crystallized with substoichiometric amounts of an NSAID, both monomers are often fully occupied with inhibitor; thus, the enzyme prefers to crystallize in a fully occupied form. In comparing the five structures, we only observe changes in the positions of residues 123-129 and residues 510-515. In cases where one monomer is fully occupied with an NSAID and the partner monomer is incompletely occupied, an alternate conformation of the loop involving residues 123-129 is seen in the partially occupied monomer. We propose, on the basis of this observation and previous cross-linking studies, that cross-talk between monomers involves this mobile 123-129 loop, which is located at the dimer interface. In ovine PGHS-1 crystallized in the absence of an NSAID, there is an alternative route for substrate entry into the COX site different than the well-known route through the membrane binding domain.


  • Organizational Affiliation

    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Prostaglandin G/H synthase 1553Ovis ariesMutation(s): 0 
Gene Names: COX1PTGS1
EC: 1.14.99.1
UniProt
Find proteins for P05979 (Ovis aries)
Explore P05979 
Go to UniProtKB:  P05979
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05979
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Prostaglandin G/H synthase 1553Ovis ariesMutation(s): 0 
Gene Names: PTGS1COX1
EC: 1.14.99.1
UniProt
Find proteins for P05979 (Ovis aries)
Explore P05979 
Go to UniProtKB:  P05979
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05979
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C, F
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G07375KG
GlyCosmos:  G07375KG
GlyGen:  G07375KG
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42831WZ
GlyCosmos:  G42831WZ
GlyGen:  G42831WZ
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
G
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G62182OO
GlyCosmos:  G62182OO
GlyGen:  G62182OO
Entity ID: 7
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
H
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G35926TG
GlyCosmos:  G35926TG
GlyGen:  G35926TG
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 182.483α = 90
b = 182.483β = 90
c = 103.095γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2010-07-28 
  • Deposition Author(s): Sidhu, R.S.

Revision History  (Full details and data files)

  • Version 1.0: 2010-07-28
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Structure summary
  • Version 2.1: 2023-09-06
    Changes: Data collection, Database references, Refinement description, Structure summary