1CVU

CRYSTAL STRUCTURE OF ARACHIDONIC ACID BOUND TO THE CYCLOOXYGENASE ACTIVE SITE OF COX-2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.204 

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This is version 2.1 of the entry. See complete history


Literature

Structural insights into the stereochemistry of the cyclooxygenase reaction.

Kiefer, J.R.Pawlitz, J.L.Moreland, K.T.Stegeman, R.A.Hood, W.F.Gierse, J.K.Stevens, A.M.Goodwin, D.C.Rowlinson, S.W.Marnett, L.J.Stallings, W.C.Kurumbail, R.G.

(2000) Nature 405: 97-101

  • DOI: https://doi.org/10.1038/35011103
  • Primary Citation of Related Structures:  
    1CVU, 1DDX

  • PubMed Abstract: 

    Cyclooxygenases are bifunctional enzymes that catalyse the first committed step in the synthesis of prostaglandins, thromboxanes and other eicosanoids. The two known cyclooxygenases isoforms share a high degree of amino-acid sequence similarity, structural topology and an identical catalytic mechanism. Cyclooxygenase enzymes catalyse two sequential reactions in spatially distinct, but mechanistically coupled active sites. The initial cyclooxygenase reaction converts arachidonic acid (which is achiral) to prostaglandin G2 (which has five chiral centres). The subsequent peroxidase reaction reduces prostaglandin G2 to prostaglandin H2. Here we report the co-crystal structures of murine apo-cyclooxygenase-2 in complex with arachidonic acid and prostaglandin. These structures suggest the molecular basis for the stereospecificity of prostaglandin G2 synthesis.


  • Organizational Affiliation

    Searle Discovery Research, Monsanto Company, St Louis, Missouri 63198, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROSTAGLANDIN H2 SYNTHASE-2
A, B
552Mus musculusMutation(s): 2 
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
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (9-MER)C [auth F]9N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseD [auth C],
F [auth E]
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseE [auth D],
G
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G04854NQ
GlyCosmos:  G04854NQ
GlyGen:  G04854NQ
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ACD
Query on ACD

Download Ideal Coordinates CCD File 
L [auth A],
P [auth B]
ARACHIDONIC ACID
C20 H32 O2
YZXBAPSDXZZRGB-DOFZRALJSA-N
BOG
Query on BOG

Download Ideal Coordinates CCD File 
I [auth A],
J [auth A],
K [auth A],
N [auth B],
O [auth B]
octyl beta-D-glucopyranoside
C14 H28 O6
HEGSGKPQLMEBJL-RKQHYHRCSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
H [auth A],
M [auth B]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ACD BindingDB:  1CVU Kd: 8070 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.204 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 181.036α = 90
b = 133.96β = 90
c = 124.834γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
X-PLORmodel building
X-PLORrefinement
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2000-05-16
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2021-11-03
    Changes: Database references, Structure summary