{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Amaya JA"],"funding":["NIH","NIGMS NIH HHS"],"pagination":["101746"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8960966"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["298(4)"],"pubmed_abstract":["AmphL is a cytochrome P450 enzyme that catalyzes the C8 oxidation of 8-deoxyamphotericin B to the polyene macrolide antibiotic, amphotericin B. To understand this substrate selectivity, we solved the crystal structure of AmphL to a resolution of 2.0 Å in complex with amphotericin B and performed molecular dynamics (MD) simulations. A detailed comparison with the closely related P450, PimD, which catalyzes the epoxidation of 4,5-desepoxypimaricin to the macrolide antibiotic, pimaricin, reveals key catalytic structural features responsible for stereo- and regio-selective oxidation. Both P450s have a similar access channel that runs parallel to the active site I helix over the surface of the heme. Molecular dynamics simulations of substrate binding reveal PimD can \"pull\" substrates further in"],"journal":["The Journal of biological chemistry"],"pubmed_title":["Structural analysis of P450 AmphL from Streptomyces nodosus provides insights into substrate selectivity of polyene macrolide antibiotic biosynthetic P450s."],"pmcid":["PMC8960966"],"funding_grant_id":["R35 GM131920","P30 GM133894"],"pubmed_authors":["Caffrey P","Poulos TL","Amaya JA","Murarka VC","Kelly SL","Lamb DC"],"additional_accession":[]},"is_claimable":false,"name":"Structural analysis of P450 AmphL from Streptomyces nodosus provides insights into substrate selectivity of polyene macrolide antibiotic biosynthetic P450s.","description":"AmphL is a cytochrome P450 enzyme that catalyzes the C8 oxidation of 8-deoxyamphotericin B to the polyene macrolide antibiotic, amphotericin B. To understand this substrate selectivity, we solved the crystal structure of AmphL to a resolution of 2.0 Å in complex with amphotericin B and performed molecular dynamics (MD) simulations. A detailed comparison with the closely related P450, PimD, which catalyzes the epoxidation of 4,5-desepoxypimaricin to the macrolide antibiotic, pimaricin, reveals key catalytic structural features responsible for stereo- and regio-selective oxidation. Both P450s have a similar access channel that runs parallel to the active site I helix over the surface of the heme. Molecular dynamics simulations of substrate binding reveal PimD can \"pull\" substrates further in","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-31T21:01:23.4Z","creation":"2025-02-19T04:22:14.449Z"},"accession":"S-EPMC8960966","cross_references":{"pubmed":["35189143"],"doi":["10.1016/j.jbc.2022.101746"]}}