8YXA

Crystal structure of the HSA complex with cefazolin and myristate

Summary for 8YXA

• Entry DOI: 10.2210/pdb8yxa/pdb
• Related: 8YXB
• Descriptor: Serum albumin, (6~{R},7~{R})-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxidanylidene-7-[2-(1,2,3,4-tetrazol-1-yl)ethanoylamino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, MYRISTIC ACID (3 entities in total)
• Functional Keywords: human serum albumin, antibiotics complex, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 135193.31

Authors

Kawai, A. (deposition date: 2024-04-02, release date: 2024-08-07, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)