3A73

Crystal Structure Analysis of Human serum albumin complexed with delta 12-prostaglandin J2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.19 Å
  • R-Value Free: 0.291 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.233 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Delta12-prostaglandin J2 as a product and ligand of human serum albumin: formation of an unusual covalent adduct at His146.

Yamaguchi, S.Aldini, G.Ito, S.Morishita, N.Shibata, T.Vistoli, G.Carini, M.Uchida, K.

(2010) J Am Chem Soc 132: 824-832

  • DOI: https://doi.org/10.1021/ja908878n
  • Primary Citation of Related Structures:  
    3A73

  • PubMed Abstract: 

    Human serum albumin (HSA), the most abundant protein in plasma, has a very unique function, catalyzing the conversion of prostaglandin J(2) (PGJ(2)), a dehydration product of PGD(2), to yield Delta(12)-PGJ(2). These PGD(2) metabolites are actively transported into cells and accumulated in the nuclei, where they act as potent inducers of cell growth inhibition and cell differentiation, and exhibit their own unique spectrum of biological effects. The facts that (i) arachidonic acid metabolites bind to human serum albumin (HSA) and the metabolism of these molecules is altered as a result of binding, (ii) HSA catalyzes the transformation of PGJ(2) into Delta(12)-PGJ(2), and (iii) Delta(12)-PGJ(2) is stable in serum suggest that HSA may bind and stabilize Delta(12)-PGJ(2) in a specific manner. A molecular interaction analysis using surface plasmon resonance (Biacore) indeed suggested the presence of a specific Delta(12)-PGJ(2)-binding site in HSA. To investigate the molecular details of the binding of this PGD(2) metabolite to albumin, we analyzed the cocrystal structure of the HSA-Delta(12)-PGJ(2)-myristate complex by X-ray crystallography and found that two Delta(12)-PGJ(2) molecules bind to a primary site in subdomain IB of the protein. The electron density results suggested that one of the two Delta(12)-PGJ(2) molecules that specifically bind to the site covalently interacted with a histidine residue (His146). Using nano-LC-MS/MS analysis of the HSA-Delta(12)-PGJ(2) complex, the formation of an unusual Delta(12)-PGJ(2)-histidine adduct at His146 was confirmed. Thus, our crystallographic and mass spectrometric analyses of the HSA-Delta(12)-PGJ(2) complex provided intriguing new insights into the molecular details of how this electrophilic ligand interacts with its primary producer and transporter.


  • Organizational Affiliation

    Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serum albumin
A, B
585Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P02768 (Homo sapiens)
Explore P02768 
Go to UniProtKB:  P02768
PHAROS:  P02768
GTEx:  ENSG00000163631 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP02768
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PJ2
Query on PJ2

Download Ideal Coordinates CCD File 
I [auth A],
J [auth A],
Q [auth B]
(5Z,12Z,15S)-15-hydroxy-11-oxoprosta-5,9,12-trien-1-oic acid
C20 H30 O4
TUXFWOHFPFBNEJ-WHYHPIPXSA-N
MYR
Query on MYR

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
K [auth B],
L [auth B],
M [auth B],
N [auth B],
O [auth B],
P [auth B]
MYRISTIC ACID
C14 H28 O2
TUNFSRHWOTWDNC-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
PJ2 PDBBind:  3A73 Kd: 4.20e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.19 Å
  • R-Value Free: 0.291 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.233 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.06α = 74.8
b = 92.047β = 89.53
c = 94.664γ = 80.21
Software Package:
Software NamePurpose
HKL-2000data collection
MLPHAREphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2010-01-19 
  • Deposition Author(s): Ito, S.

Revision History  (Full details and data files)

  • Version 1.0: 2010-01-19
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2013-10-23
    Changes: Database references
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description