https://www.embl-hamburg.de/biosaxs/reprints/gasbor_2001.pdf

Determination of domain structure of proteins from X-ray solution scattering.

Human serum albumin: from bench to bedside.

In healthy humans, the incretin glucagon-like peptide 1 (GLP-1) is secreted after eating and lowers glucose concentrations by augmenting insulin secretion and suppressing glucagon release. Additional effects of GLP-1 include retardation of gastric emptying, suppression of appetite and, potentially, inhibition of β-cell apoptosis. Native GLP-1 is degraded within ~2-3 min in the circulation; various GLP-1 receptor agonists have, therefore, been developed to provide prolonged in vivo actions. These GLP-1 receptor agonists can be categorized as either short-acting compounds, which provide short-lived receptor activation (such as exenatide and lixisenatide) or as long-acting compounds (for example albiglutide, dulaglutide, exenatide long-acting release, and liraglutide), which activate the GLP-1 receptor continuously at their recommended dose. The pharmacokinetic differences between these drugs lead to important differences in their pharmacodynamic profiles. The short-acting GLP-1 receptor agonists primarily lower postprandial blood glucose levels through inhibition of gastric emptying, whereas the long-acting compounds have a stronger effect on fasting glucose levels, which is mediated predominantly through their insulinotropic and glucagonostatic actions. The adverse effect profiles of these compounds also differ. The individual properties of the various GLP-1 receptor agonists might enable incretin-based treatment of type 2 diabetes mellitus to be tailored to the needs of each patient.

GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus.

Human serum albumin (HSA), the most prominent protein in plasma, binds different classes of ligands at multiple sites HSA provides a depot for many compounds, affects pharmacokinetics of many drugs, holds some ligands in a strained orientation providing their metabolic modification, renders potential toxins harmless transporting them to disposal sites, accounts for most of the antioxidant capacity of human serum, and acts as a NO-carrier The globular domain structural organization of monomeric HSA is at the root of its allosteric properties which are reminiscent of those of multimeric proteins Here, structural, functional, biotechnological, and biomedical aspects of ligand binding to HSA are summarized

https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1080/15216540500404093

The extraordinary ligand binding properties of human serum albumin

Crystallographic Analysis Reveals Common Modes of Binding of Medium and Long-Chain Fatty Acids to Human Serum Albumin

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.

S. Sugio

Papers

Crystal structure of human serum albumin at 2.5 A resolution.

Crystal structure of human serum albumin