Crystal structures of serum albumins from domesticated ruminants and their complexes with 3,5-diiodosalicylic acid

Abstract

Serum albumin (SA) is the most abundant protein in plasma and is the main transporter of molecules in the circulatory system of all vertebrates, with applications in medicine, the pharmaceutical industry and molecular biology. It is known that albumins from different organisms vary in sequence; thus, it is important to know the impact of the amino-acid sequence on the three-dimensional structure and ligand-binding properties. Here, crystal structures of ovine (OSA) and caprine (CSA) serum albumins, isolated from sheep and goat blood, are described, as well those of their complexes with 3,5-diiodosalicylic acid (DIS): OSA-DIS (2.20 Å resolution) and CSA-DIS (1.78 Å resolution). The ligand-free OSA structure was determined in the trigonal space group P321 at 2.30 Å resolution, while that of CSA in the orthorhombic space group P222 was determined at 1.94 Å resolution. Both albumins are also capable of crystallizing in the triclinic space group P1, giving isostructural crystals that diffract to around 2.5 Å resolution. A comparison of OSA and CSA with the closely related bovine serum albumin (BSA) shows both similarities and differences in the distribution of DIS binding sites. The investigated serum albumins from domesticated ruminants in their complexes with DIS are also compared with the analogous structures of equine and human serum albumins (ESA-DIS and HSA-DIS). Surprisingly, despite 98% sequence similarity, OSA binds only two molecules of DIS, whereas CSA binds six molecules of this ligand. Moreover, the binding of DIS to OSA and CSA introduced changes in the overall architecture of the proteins, causing not only different conformations of the amino-acid side chains in the binding pockets, but also a significant shift of the whole helices, changing the volume of the binding cavities.

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

“…Previously, it was assumed that the albumin molecule had the shape of an elongated or flattened ellipsoid (“cigar” or “pill”), but X-ray analysis showed that the protein has the shape of a heart. In addition to HSA, three-dimensional structures of BSA [ 61 ], albumin of horse and rabbit [ 61 ], sheep and goat [ 62 ], dogs [ 63 ] and cats [ 64 ] have been obtained so far.…”

Concentration Dependences of Macromolecular Sizes in Aqueous Solutions of Albumins

“…Serum albumins are globular proteins, each consisting of a sequence of amino acid residues that are linked into a single-stranded macromolecule with a rather complicated spatial structure [1]. The functional properties of albumin macromolecules depend on their spatial structures at the secondary and tertiary levels, which are determined by the specific sequence of amino acids in the molecular chain [1,2]. The secondary structure of an albumin macromolecule consists of alpha-helices and beta-folds sta-bilized by hydrogen bonds, and a disordered part of the macromolecular chain.…”

“…The secondary structure of an albumin macromolecule consists of alpha-helices and beta-folds sta-bilized by hydrogen bonds, and a disordered part of the macromolecular chain. The tertiary structure of an albumin macromolecule is represented by its domain composition, with hydrophobic interactions between the domains being responsible for the globular structure of the protein [1][2][3].…”

Capturing and Stabilizing Folded Proteins in Lattices Formed with Branched Oligonucleotide Hybrids

“… Structures of components employed in encapsulation assays, roughly drawn to scale. For proteins, the structures were generated from PDB IDs: 2KY8 (Mbd2, 3.7 nm/10 kDa), 4NW3 (CxxC, 3.2 nm/11 kDa), 5TY3 (cytochrome c , 3.8 nm/12 kDa), 1GFL (GFP, 3,8 nm/27 kDa), 2CAB (carbonic anhydrase, 4.3 nm/29 kDa), 4LUF (albumin, 8.3 nm/68 kDa), 1ALD (aldolase, 11 nm/159 kDa), 1FA2 (amylase, 12 nm/226 kDa), and 1LB3 (ferritin, 13 nm/529 kDa). For double‐stranded DNA, a canonical B‐form duplex was generated in Maestro, version 7.5.106; for hybrid 2 , an energy‐minimized structure generated in Chem3D Pro, version 14.0, is shown.…”