PDBsum entry 5iih

Transport protein

PDB id: 5iih

Contents

Protein chain

580 a.a.

Ligands

SO4

Metals

_ZN

Waters ×133

PDB id:

5iih

Name:

Transport protein

Title:

Crystal structure of equine serum albumin in the presence of 2.5 mm zinc at ph 7.4

Structure:

Serum albumin. Chain: a. Fragment: residues 25-607

Source:

Equus caballus. Horse. Organism_taxid: 9796

Resolution:

2.40Å R-factor: 0.178 R-free: 0.235

Authors:

K.B.Handing,I.G.Shabalin,D.R.Cooper,S.C.Almo,W.Minor,New York Structural Genomics Research Consortium (Nysgrc)

Key ref:

K.B.Handing et al. (2016). Circulatory zinc transport is controlled by distinct interdomain sites on mammalian albumins. Chem Sci, 7, 6635-6648. PubMed id: 28567254

Date:

01-Mar-16 Release date: 16-Mar-16

Protein chain

P35747  (ALBU_HORSE) -  Albumin from Equus caballus

Seq: 607 a.a.

Struc: 580 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Chem Sci 7:6635-6648 (2016)

PubMed id: 28567254

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

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

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.