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J Biol Chem. 2009 Aug 21;284(34):23116-24. doi: 10.1074/jbc.M109.003459. Epub 2009 Jun 11.

Structure, properties, and engineering of the major zinc binding site on human albumin.

Author information

1
Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, United Kingdom. c.blindauer@warwick.ac.uk

Abstract

Most blood plasma zinc is bound to albumin, but the structure of the binding site has not been determined. Zn K-edge extended x-ray absorption fine structure spectroscopy and modeling studies show that the major Zn(2+) site on albumin is a 5-coordinate site with average Zn-O/N distances of 1.98 A and a weak sixth O/N bond of 2.48 A, consistent with coordination to His(67) and Asn(99) from domain I, His(247) and Asp(249) from domain II (residues conserved in all sequenced mammalian albumins), plus a water ligand. The dynamics of the domain I/II interface, thought to be important to biological function, are affected by Zn(2+) binding, which induces cooperative allosteric effects related to those of the pH-dependent neutral-to-base transition. N99D and N99H mutations enhance Zn(2+) binding but alter protein stability, whereas mutation of His(67) to alanine removes an interdomain H-bond and weakens Zn(2+) binding. Both wild-type and mutant albumins promote the safe management of high micromolar zinc concentrations for cells in cultures.

PMID:
19520864
PMCID:
PMC2755717
DOI:
10.1074/jbc.M109.003459
[Indexed for MEDLINE]
Free PMC Article

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