6M5D

Human serum albumin (apo form)

6M5D の概要

• エントリーDOI: 10.2210/pdb6m5d/pdb
• 分子名称: Serum albumin, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: transporter, cyclic peptide, peptide binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 66057.52

構造登録者

Ito, S.,Senoo, A.,Nagatoishi, S.,Yamamoto, M.,Tsumoto, K.,Wakui, N. (登録日: 2020-03-10, 公開日: 2020-11-18, 最終更新日: 2024-11-13)

主引用文献

Ito, S.,Senoo, A.,Nagatoishi, S.,Ohue, M.,Yamamoto, M.,Tsumoto, K.,Wakui, N.
Structural Basis for the Binding Mechanism of Human Serum Albumin Complexed with Cyclic Peptide Dalbavancin.
J.Med.Chem., 63:14045-14053, 2020

PubMed Abstract: Cyclic peptides, with unique structural features, have emerged as new candidates for drug discovery; their association with human serum albumin (HSA; long blood half-life) is crucial to improve drug delivery and avoid renal clearance. Here, we present the crystal structure of HSA complexed with dalbavancin, a clinically used cyclic peptide. Small-angle X-ray scattering and isothermal titration calorimetry experiments showed that the HSA-dalbavancin complex exists in a monomeric state; dalbavancin is only bound to the subdomain IA of HSA in solution. Structural analysis and MD simulation revealed that the swing of Phe70 and movement of the helix near dalbavancin were necessary for binding. The flip of Leu251 promoted the formation of the binding pocket with an induced-fit mechanism; moreover, the movement of the loop region including Glu60 increased the number of noncovalent interactions with HSA. These findings may support the development of new cyclic peptides for clinical use, particularly the elucidation of their binding mechanism to HSA.

PubMed: 33183011
DOI: 10.1021/acs.jmedchem.0c01578

実験手法

X-RAY DIFFRACTION (2.6 Å)