5V0V

Crystal structure of Equine Serum Albumin complex with etodolac


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Albumin-Based Transport of Nonsteroidal Anti-Inflammatory Drugs in Mammalian Blood Plasma.

Czub, M.P.Handing, K.B.Venkataramany, B.S.Cooper, D.R.Shabalin, I.G.Minor, W.

(2020) J Med Chem 

  • DOI: https://doi.org/10.1021/acs.jmedchem.0c00225
  • Primary Citation of Related Structures:  
    5V0V, 6CI6, 6U4R, 6U4X, 6U5A

  • PubMed Abstract: 

    Every day, hundreds of millions of people worldwide take nonsteroidal anti-inflammatory drugs (NSAIDs), often in conjunction with multiple other medications. In the bloodstream, NSAIDs are mostly bound to serum albumin (SA). We report the crystal structures of equine serum albumin complexed with four NSAIDs (ibuprofen, ketoprofen, etodolac, and nabumetone) and the active metabolite of nabumetone (6-methoxy-2-naphthylacetic acid, 6-MNA). These compounds bind to seven drug-binding sites on SA. These sites are generally well-conserved between equine and human SAs, but ibuprofen binds to both SAs in two drug-binding sites, only one of which is common. We also compare the binding of ketoprofen by equine SA to binding of it by bovine and leporine SAs. Our comparative analysis of known SA complexes with FDA-approved drugs clearly shows that multiple medications compete for the same binding sites, indicating possibilities for undesirable physiological effects caused by drug-drug displacement or competition with common metabolites. We discuss the consequences of NSAID binding to SA in a broader scientific and medical context, particularly regarding achieving desired therapeutic effects based on an individual's drug regimen.


  • Organizational Affiliation

    Department of Molecular Physiology and Biological Physics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, Virginia 22908, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serum albumin583Equus caballusMutation(s): 0 
UniProt
Find proteins for P35747 (Equus caballus)
Explore P35747 
Go to UniProtKB:  P35747
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35747
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
8QS
Query on 8QS

Download Ideal Coordinates CCD File 
O [auth A],
P [auth A]
[(1R)-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl]acetic acid
C17 H21 N O3
NNYBQONXHNTVIJ-QGZVFWFLSA-N
8QP
Query on 8QP

Download Ideal Coordinates CCD File 
M [auth A],
N [auth A]
[(1S)-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl]acetic acid
C17 H21 N O3
NNYBQONXHNTVIJ-KRWDZBQOSA-N
TRS
Query on TRS

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A],
D [auth A],
E [auth A]
2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
C4 H12 N O3
LENZDBCJOHFCAS-UHFFFAOYSA-O
SO4
Query on SO4

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
H [auth A]
I [auth A]
J [auth A]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 
  • Space Group: P 61
  • Diffraction Data: https://doi.org/10.18430/M35V0V
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 94.209α = 90
b = 94.209β = 90
c = 141.819γ = 120
Software Package:
Software NamePurpose
HKL-3000data reduction
MOLREPphasing
HKL-3000phasing
REFMACrefinement
PDB_EXTRACTdata extraction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01-GM117080
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01-GM118619
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01-GM132595

Revision History  (Full details and data files)

  • Version 1.0: 2017-03-15
    Type: Initial release
  • Version 1.1: 2017-09-13
    Changes: Author supporting evidence
  • Version 1.2: 2020-07-15
    Changes: Database references
  • Version 1.3: 2022-04-13
    Changes: Author supporting evidence, Database references
  • Version 1.4: 2023-10-04
    Changes: Data collection, Refinement description