King Abdullah University of Science and Technology (KAUST), Biological and Environmental Science and Engineering Division (BESE), 23955-6900 Thuwal, Saudi Arabia.
Dipartimento di Scienze Chimiche e Geologiche, Università di Cagliari, Cittadella Universitaria, I-09042 Monserrato, Cagliari, Italy.
J Inorg Biochem. 2019 Sep;198:110716. doi: 10.1016/j.jinorgbio.2019.110716. Epub 2019 May 20.
Human serum albumin (HSA) is a monomeric, globular, multi-carrier and the most abundant protein in the blood. HSA displays multiple ligand binding sites with extraordinary binding capacity for a wide range of ions and molecules. For decades, HSA's ability to bind to various ligands has led many scientists to study its physiological properties and protein structure; indeed, a better understanding of HSA-ligand interactions in human blood, at the atomic level, will likely foster the development of more potent, and overall more performant, diagnostic and therapeutic tools against serious human disorders such as diabetes, cardiovascular disorders, and cancer. Here, we present a concise overview of the current knowledge of HSA's structural characteristics, and its coordination chemistry with transition metal ions, within the scope and limitations of current techniques and biophysical methods to reach atomic resolution in solution and in blood serum. We also highlight the overwhelming need of a detailed atomistic understanding of HSA dynamic structures and interactions that are transient, weak, multi-site and multi-step, and allosterically affected by each other. Considering the fact that HSA is a current clinical tool for drug delivery systems and a potential contender as molecular cargo and nano-vehicle used in biophysical, clinical and industrial fields, we underline the emerging need for novel approaches to target the dynamic functional coordination chemistry of the human blood serum albumin in solution, at the atomic level.
人血清白蛋白（HSA）是一种单体、球形、多功能的蛋白质，也是血液中最丰富的蛋白质。HSA 具有多个配体结合位点，具有非凡的结合能力，可以结合广泛的离子和分子。几十年来，HSA 结合各种配体的能力促使许多科学家研究其生理特性和蛋白质结构；事实上，更好地了解人血液中 HSA-配体相互作用，在原子水平上，可能会促进开发更有效、更全面的诊断和治疗工具，以对抗糖尿病、心血管疾病和癌症等严重人类疾病。在这里，我们简要概述了 HSA 的结构特征及其与过渡金属离子的配位化学，范围和限制在当前技术和生物物理方法内，以达到溶液和血清中的原子分辨率。我们还强调了对 HSA 动态结构和相互作用的详细原子理解的巨大需求，这些结构和相互作用是瞬态的、弱的、多部位的和多步骤的，并且彼此相互变构影响。考虑到 HSA 是药物输送系统的当前临床工具，并且作为生物物理、临床和工业领域中使用的分子货物和纳米载体有潜在的竞争者，我们强调了需要新方法来针对溶液中 HSA 的动态功能配位化学，达到原子水平。
