8YXB

Crystal structure of the HSA complex with ceftriaxone and myristate

8YXB の概要

• エントリーDOI: 10.2210/pdb8yxb/pdb
• 関連するPDBエントリー: 8yxa
• 分子名称: Serum albumin, Ceftriaxone, MYRISTIC ACID, ... (4 entities in total)
• 機能のキーワード: human serum albumin, antibiotics complex, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 136763.68

構造登録者

Kawai, A. (登録日: 2024-04-02, 公開日: 2024-08-07, 最終更新日: 2024-10-30)

主引用文献

Kawai, A.,Yamasaki, K.,Otagiri, M.,Doi, Y.
Interaction of Cephalosporins with Human Serum Albumin: A Structural Study.
J.Med.Chem., 67:14175-14183, 2024

PubMed Abstract: Modification of the R1 and R2 side chain structures has been used as the main strategy to expand the spectrum of cephalosporins and impart resistance to hydrolysis by β-lactamases. These structural modifications also result in a wide range of plasma protein binding, especially with human serum albumin (HSA). Here, we determined the crystal structures of the HSA complexes with two clinically important cephalosporins, ceftriaxone and cefazolin, and evaluated the binding of cephalosporin to HSA by susceptibility testing and competitive binding assay. Ceftriaxone and cefazolin bind to subdomain IB of HSA, and their cephem core structures are recognized by Arg117 of HSA. Tyr161 of HSA changes its rotamer depending on the cephalosporin, resulting in alterations of the cavity shape occupied by the R2 side chain of cephalosporins. These findings provide structural insight into the mechanisms underlying the HSA binding of cephalosporins.

PubMed: 39083648
DOI: 10.1021/acs.jmedchem.4c00983

実験手法

X-RAY DIFFRACTION (2.2 Å)