title: Understanding the effects of two bound glucose in Sudlow site I on structure and function of human serum albumin: theoretical studies.
abstract: Human serum albumin (HSA) is the most abundant protein found in blood serum. It carries essential metabolites and many drugs. The glycation of HSA causes abnormal biological effects. Importantly, glycated HSA (GHSA) is of interest as a biomarker for diabetes. Recently, the first HSA structure with bound pyranose (GLC) and open-chain (GLO) glucose at Sudlow site I has been crystallised. We therefore employed molecular dynamics (MD) simulations and ONIOM calculations to study the dynamic nature of two bound glucose in a pre-glycated HSA (pGHSA) and observe how those sugars alter a protein structure comparing to wild type (Apo) and fatty acid-bound HSA (FA). Our analyses show that the overall structural stability of pGHSA is similar to Apo and FA, except Sudlow site II. Having glucose induces large protein flexibility at Sudlow site II. Besides, the presence of glucose causes W214 to reorient resulting in a change in W214 microenvironment. Considering sugars, both sugars are exposed to water, but GLO is more solvent-accessible. ONIOM results show that glucose binding is favoured for HSA (-115.04 kcal/mol) and GLO (-85.10 kcal/mol) is more preferable for Sudlow site I over GLC (-29.94 kcal/mol). GLO can strongly react with K195 and K199, whereas K195 and K199 provide slightly repulsive forces for GLC. This can confirm that an open-chain GLO is more favourable inside a pocket.
authors.affiliation: a Faculty of Science, Department of Chemistry , Prince of Songkla University , Hatyai , Songkla 90112 , Thailand.
authors.forename: Tadsanee
authors.initials: T
authors.lastname: Awang
authors.affiliation: b Faculty of Science, Department of Chemistry , Kasetsart University , Chatuchak , Bangkok 10900 , Thailand.
authors.forename: Nuttapon
authors.initials: N
authors.lastname: Wiriyatanakorn
authors.affiliation: b Faculty of Science, Department of Chemistry , Kasetsart University , Chatuchak , Bangkok 10900 , Thailand.
authors.forename: Patchreenart
authors.initials: P
authors.lastname: Saparpakorn
authors.affiliation: c National Nanotechnology Center , National Science and Technology Development Agency , Thailand Science Park, Pathumthani 12120 , Thailand.
authors.forename: Deanpen
authors.initials: D
authors.lastname: Japrung
authors.affiliation: b Faculty of Science, Department of Chemistry , Kasetsart University , Chatuchak , Bangkok 10900 , Thailand.|d Center for Advanced Studies in Nanotechnology and its Applications in Chemical, Food and Agricultural Industries , Kasetsart University , Bangkok 10900 , Thailand.|e Computational Biomodelling Laboratory for Agricultural Science and Technology (CBLAST) , Kasetsart University , Bangkok 10900 , Thailand.
authors.forename: Prapasiri
authors.initials: P
authors.lastname: Pongprayoon
mesh_terms: D001665:Binding Sites; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D012709:Serum Albumin; D005947:Glucose
keywords: glucose; glycated human serum albumin; human serum albumin; molecular dynamics simulations