Structure-based selection of human metabolite binding P4 pocket of DRB1*15:01 and DRB1*15:03, with implications for multiple sclerosis.

ABSTRACT: Binding of small molecules in the human leukocyte antigen (HLA) peptide-binding groove may result in conformational changes of bound peptide and an altered immune response, but previous studies have not considered a potential role for endogenous metabolites. We performed virtual screening of the complete Human Metabolite Database (HMDB) for docking to the multiple sclerosis (MS) susceptible DRB1*15:01 allele and compared the results to the closely related yet non-susceptible DRB1*15:03 allele; and assessed the potential impact on binding of human myelin basic peptide (MBP). We observed higher energy scores for metabolite binding to DRB1*15:01 than DRB1*15:03. Structural comparison of docked metabolites with DRB1*15:01 and DRB1*15:03 complexed with MBP revealed that Phenylalanine^MBP92<

SUBMITTER: Misra MK 

PROVIDER: S-EPMC6054566 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature