Crystal structure of human serum albumin at 2.5 Å resolution

Abstract

A new triclinic crystal form of human serum albumin (HSA), derived either from pool plasma (pHSA) or from a Pichia pastoris expression system (rHSA), was obtained from polyethylene glycol 4000 solution. Three-dimensional structures of pHSA and rHSA were determined at 2.5 A resolution from the new triclinic crystal form by molecular replacement, using atomic coordinates derived from a multiple isomorphous replacement work with a known tetragonal crystal form. The structures of pHSA and rHSA are virtually identical, with an r.m. s. deviation of 0.24 A for all Calpha atoms. The two HSA molecules involved in the asymmetric unit are related by a strict local twofold symmetry such that the Calpha atoms of the two molecules can be superimposed with an r.m.s. deviation of 0.28 A in pHSA. Cys34 is the only cysteine with a free sulfhydryl group which does not participate in a disulfide linkage with any external ligand. Domains II and III both have a pocket formed mostly of hydrophobic and positively charged residues and in which a very wide range of compounds may be accommodated. Three tentative binding sites for long-chain fatty acids, each with different surroundings, are located at the surface of each domain.

Evidence for pH-dependent multiple conformers in iron(II) heme–human serum albumin: spectroscopic and kinetic investigation of carbon monoxide binding

“…Terminal regions of sequential domains contribute to the formation of interdomain h10-h1 helices linking subdomain IB to subdomain IIA and subdomain IIB to subdomain IIIA, respectively ( Fig. 1) [2,3,[10][11][12][13][14][15][16][17].…”

A fluorescent fatty acid probe, DAUDA, selectively displaces two myristates bound in human serum albumin

“…Each domain contains 10 helices and is divided into anti-parallel six-helix and four-helix subdomains (A and B). 7 The X-ray structural studies showed that these two primary drug sites (Sudlow's site I and II) 8,9 are located in the subdomain IIA and subdomain IIIA, respectively. 10 We and others have shown that Sudlow site I at subdomain IIA is a large binding pocket and can be further divided into three non-overlapping subsites.…”

Nonimmunogenetic Viral Capsid Carrier with Cancer Targeting Activity

“…The albumin‐binding activity of ABP‐HBVC was further monitored through time‐course dynamic light scattering (DLS) analysis after ABP‐HBVC (or ABP‐free HBVC) was added to human serum (Figure 2B,C). The particle size of ABP‐free HBVC (indicated by blue dotted circles in Figure 2B) never changed for 24 h in human serum, while both of the DLS peaks for ABP‐HBVC and HSA (that are present as a dimer having the size of ≈14 nm,24, 25 indicated by red dotted circles in Figure 2C) disappeared, and the new peaks around 50 nm (indicated by red arrows in Figure 2C) newly appeared immediately after ABP‐HBVC was added to human serum, showing clearly the binding between ABP‐HBVC and serum albumins. We also measured the amount of E. coli ‐derived endotoxin (LPS) involved in the purified ABP‐HBVC and ABP‐free HBVC.…”