1FV0

FIRST STRUCTURAL EVIDENCE OF THE INHIBITION OF PHOSPHOLIPASE A2 BY ARISTOLOCHIC ACID: CRYSTAL STRUCTURE OF A COMPLEX FORMED BETWEEN PHOSPHOLIPASE A2 AND ARISTOLOCHIC ACID


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.212 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history


Literature

Structural Basis of Phospholipase A2 Inhibition for the Synthesis of Prostaglandins by the Plant Alkaloid Aristolochic Acid from a 1.7 A Crystal Structure

Chandra, V.Jasti, J.Kaur, P.Srinivasan, A.Betzel, C.Singh, T.P.

(2002) Biochemistry 41: 10914-10919

  • DOI: https://doi.org/10.1021/bi0258593
  • Primary Citation of Related Structures:  
    1FV0

  • PubMed Abstract: 

    This is the first structural observation of a plant product showing high affinity for phospholipase A(2) and regulating the synthesis of arachidonic acid, an intermediate in the production of prostaglandins. The crystal structure of a complex formed between Vipera russelli phospholipase A(2) and a plant alkaloid aristolochic acid has been determined and refined to 1.7 A resolution. The structure contains two crystallographically independent molecules of phospholipase A(2) in the form of an asymmetric dimer with one molecule of aristolochic acid bound to one of them specifically. The most significant differences introduced by asymmetric molecular association in the structures of two molecules pertain to the conformations of their calcium binding loops, beta-wings, and the C-terminal regions. These differences are associated with a unique conformational behavior of Trp(31). Trp(31) is located at the entrance of the characteristic hydrophobic channel which works as a passage to the active site residues in the enzyme. In the case of molecule A, Trp(31) is found at the interface of two molecules and it forms a number of hydrophobic interactions with the residues of molecule B. Consequently, it is pulled outwardly, leaving the mouth of the hydrophobic channel wide open. On the other hand, Trp(31) in molecule B is exposed to the surface and moves inwardly due to the polar environment on the molecular surface, thus narrowing the opening of the hydrophobic channel. As a result, the aristolochic acid is bound to molecule A only while the binding site of molecule B is empty. It is noteworthy that the most critical interactions in the binding of aristolochic acid are provided by its OH group which forms two hydrogen bonds, one each with His(48) and Asp(49).


  • Organizational Affiliation

    Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PHOSPHOLIPASE A2
A, B
121Daboia russelii pulchellaMutation(s): 0 
UniProt
Find proteins for P59071 (Daboia russelii)
Explore P59071 
Go to UniProtKB:  P59071
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP59071
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
9AR
Query on 9AR

Download Ideal Coordinates CCD File 
F [auth A]9-HYDROXY ARISTOLOCHIC ACID
C17 H11 N O8
UCLGCTLOEZZSLA-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
H [auth B],
I [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth A],
L [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
DIO
Query on DIO

Download Ideal Coordinates CCD File 
J [auth B],
K [auth B]
1,4-DIETHYLENE DIOXIDE
C4 H8 O2
RYHBNJHYFVUHQT-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
E [auth A]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
9AR Binding MOAD:  1FV0 Ki: 1180 (nM) from 1 assay(s)
PDBBind:  1FV0 Ki: 1180 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.212 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.05α = 90
b = 89.48β = 90
c = 76.87γ = 90
Software Package:
Software NamePurpose
MAR345data collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-08-28
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2011-11-16
    Changes: Atomic model
  • Version 1.4: 2017-10-04
    Changes: Refinement description
  • Version 1.5: 2018-01-24
    Changes: Database references
  • Version 1.6: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description