Interdomain zinc site on human albumin

• DOI: 10.1073/pnas.0436576100
• Publication Date: 2003-04-01T19:25:08Z
• Authors: Alan J. Stewart; Claudia A. Blindauer; Stephen Berezenko; Darrell Sleep; Peter J. Sadler
• Keywords: Human serum albumin; Serum Albumin

Albumin is the major transport protein in blood for Zn 2+ , a metal ion required physiological processes and recruited by various drugs toxins. However, -binding site(s) on albumin ill-defined. We have analyzed 18 x-ray crystal structures of human PDB identified potential five-coordinate site at interface domains I II consisting N ligands from His-67 His-247 O Asn-99, Asp-249, H 2 O, which are same amino acid as those zinc enzymes calcineurin, endonucleotidase, purple phosphatase. The preformed unliganded apo-albumin highly conserved mammalian albumins. used 111 Cd NMR probe binding to recombinant albumin. show that → Ala (His67Ala) mutation strongly perturbs binding, whereas mutations Cys34Ala, or His39Leu Tyr84Phe (residues may H-bond Cys-34) no effect. Weak Cl − fifth coordination was demonstrated. dramatically affected high fatty loading Analysis suggests triggers spring-lock mechanism, disengages upper (His-67/Asn-99) lower (His-247/Asp-249) halves site. These findings provide possible mechanism whereby acids (and perhaps other small molecules) could influence delivery blood.