5IIX

Crystal structure of Equine Serum Albumin in the presence of 15 mM zinc at pH 6.5


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Circulatory zinc transport is controlled by distinct interdomain sites on mammalian albumins.

Handing, K.B.Shabalin, I.G.Kassaar, O.Khazaipoul, S.Blindauer, C.A.Stewart, A.J.Chruszcz, M.Minor, W.

(2016) Chem Sci 7: 6635-6648

  • DOI: https://doi.org/10.1039/c6sc02267g
  • Primary Citation of Related Structures:  
    5IIH, 5IIU, 5IIX, 5IJ5, 5IJE, 5IJF

  • PubMed Abstract: 

    Zinc is an essential nutrient in the body; it is required for the catalytic activity of many hundreds of human enzymes and virtually all biological processes, therefore its homeostasis and trafficking is of crucial interest. Serum albumin is the major carrier of Zn 2+ in the blood and is required for its systemic distribution. Here we present the first crystal structures of human serum albumin (HSA) and equine serum albumin (ESA) in complex with Zn 2+ . The structures allow unambiguous identification of the major zinc binding site on these two albumins, as well as several further, weaker zinc binding sites. The major site in both HSA and ESA has tetrahedral geometry and comprises three protein ligands from the sidechains of His67, His247 and Asp249 and a water molecule. Isothermal titration calorimetric studies of a HSA H67A mutant confirm this to be the highest affinity Zn 2+ site. Furthermore, analysis of Zn 2+ binding to HSA and ESA proved the presence of secondary sites with 20-50-fold weaker affinities, which may become of importance under particular physiological conditions. Both calorimetry and crystallography suggest that ESA possesses an additional site compared to HSA, involving Glu153, His157 and His288. The His157 residue is replaced by Phe in HSA, incapable of metal coordination. Collectively, these findings are critical to our understanding of the role serum albumin plays in circulatory Zn 2+ handling and cellular delivery.


  • Organizational Affiliation

    Department of Molecular Physiology and Biological Physics , University of Virginia School of Medicine , PO Box 800736 , Charlottesville , VA 22908-0736 , USA . Email: wladek@iwonka.med.virginia.edu ; Tel: +1-434-243-6865.


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 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
O [auth A]
P [auth A]
Q [auth A]
R [auth A]
S [auth A]
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth A],
T [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]
C [auth A]
D [auth A]
E [auth A]
F [auth A]
B [auth A],
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
UNL
Query on UNL

Download Ideal Coordinates CCD File 
M [auth A],
N [auth A]
Unknown ligand
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.181 
  • Space Group: P 61
  • Diffraction Data: https://doi.org/10.18430/M35IIX
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 94.313α = 90
b = 94.313β = 90
c = 141.485γ = 120
Software Package:
Software NamePurpose
MD2data collection
HKL-3000data reduction
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States1R01GM117325-01
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States5U54GM094662-05
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM053163

Revision History  (Full details and data files)

  • Version 1.0: 2016-03-16
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence, Derived calculations
  • Version 1.2: 2017-12-13
    Changes: Database references
  • Version 1.3: 2022-03-23
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.4: 2022-04-13
    Changes: Database references, Structure summary
  • Version 1.5: 2023-09-27
    Changes: Data collection, Refinement description