Handing, Katarzyna B., Shabalin, Ivan G., Kassaar, Omar, Khazaipoul, Siavash, Blindauer, Claudia A., Stewart, Alan, Chruszch, Maksymilian and Minor, Wladek (2016) Circulatory zinc transport is controlled by distinct interdomain sites on mammalian albumins. Chemical Science, 2016 (7). pp. 6635-6648. doi:10.1039/C6SC02267G

PDF WRAP_c6sc02267g.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution. Download (2183Kb)

Request Changes to record.

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 Zn2+ 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 Zn2+ . 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 Zn2+ site. Furthermore, analysis of Zn2+ 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 Zn2+ handling and cellular delivery.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	Serum albumin, Homeostasis, Cells , Zinc
Journal or Publication Title:	Chemical Science
Publisher:	Royal Society of Chemistry
ISSN:	2041-6520
Official Date:	1 November 2016
Dates:	Date Event 1 November 2016 Published 15 August 2016 Available 13 August 2016 Accepted 21 May 2016 Submitted
Date of first compliant deposit:	25 August 2016
Volume:	2016
Number:	7
Page Range:	pp. 6635-6648
DOI:	10.1039/C6SC02267G
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	United States. Department of Energy, Michigan Economic Development Corporation (MEDC), Michigan Technology Tri-Corridor (TTC), National Institute for Health Research (Great Britain) (NIHR), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), British Heart Foundation
Grant number:	Contract No. DE-AC02-06CH11357, Grant 085P1000817 (MEDC) (TTC), Grants 5U54GM094662-05 and R01GM05 3163 (NIHR), Grant BB/J006467/1 (BBSRC), Grant PG/15/9/31270 (British Heart Foundation)

Request changes or add full text files to a record

Repository staff actions (login required)

View Item

Downloads