Solvent accessibility of E1α and E1β residues with known missense mutations causing pyruvate dehydrogenase complex (PDC) deficiency: Impact on PDC-E1 structure and function.

ABSTRACT: Pyruvate dehydrogenase complex deficiency is a major cause of primary lactic acidemia resulting in high morbidity and mortality, with limited therapeutic options. PDHA1 mutations are responsible for >82% of cases. The E1 component of PDC is a symmetric dimer of heterodimers (αβ/α'β') encoded by PDHA1 and PDHB. We measured solvent accessibility surface area (SASA), utilized nearest-neighbor analysis, incorporated sequence changes using mutagenesis tool in PyMOL, and performed molecular modeling with SWISS-MODEL, to investigate the impact of residues with disease-causing missense variants (DMVs) on E1 structure and function. We reviewed 166 and 13 genetically resolved cases due to PDHA1 and PDHB, respectively, from variant databases. We expanded on 102 E1α and 13 E1β nonduplicate DMVs. DMVs

SUBMITTER: Ducich NH 

PROVIDER: S-EPMC9297371 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature