{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12(1)"],"submitter":["Saha I"],"pubmed_abstract":["Heme internalization by pathogenic bacteria inside a human host to accomplish the requirement of iron for important cellular processes is of paramount importance. Despite this, the mechanism of heme import by the ATP-binding-cassette (ABC) transporter HutCD in Vibrio cholerae remains unexplored. We have performed biochemical studies on ATPase HutD and its mutants, along with molecular modelling, docking and unbiased all-atom MD simulations on lipid-solvated models of permease-ATPase complex HutCD. The results demonstrated mechanisms of ATP binding/hydrolysis and trapped transient and global conformational changes in HutCD, necessary for heme internalization. ATPase HutD forms a dimer, independent of the permease HutC. Each HutD monomer canonically binds ATP in a 1:1 stoichiometry. MD simulations demonstrated that a rotational motion of HutC dimer occurs synchronously with the inter-dimeric D-loop interactions of HutDs. F151 of TM4-TM5 loop of HutC, packs with ATP and Y15 of HutD, initiating 'cytoplasmic gate opening' which mimics an 'outward-facing' to 'inward-facing' conformational switching upon ATP hydrolysis. The simulation on 'inward-facing' HutCD culminates to an 'occluded' state. The simulation on heme-docked HutCD indicated that the event of heme release occurs in ATP-free 'inward-facing' state. Gradual conformational changes of the TM5 helices of HutC towards the 'occluded' state facilitate ejection of heme."],"journal":["Scientific reports"],"pagination":["7152"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9065009"],"repository":["biostudies-literature"],"pubmed_title":["Mechanistic insights of ABC importer HutCD involved in heme internalization by Vibrio cholerae."],"pmcid":["PMC9065009"],"pubmed_authors":["Ghosh B","Dasgupta J","Agarwal S","Saha I","Mukherjee P","Chakraborty S"],"additional_accession":[]},"is_claimable":false,"name":"Mechanistic insights of ABC importer HutCD involved in heme internalization by Vibrio cholerae.","description":"Heme internalization by pathogenic bacteria inside a human host to accomplish the requirement of iron for important cellular processes is of paramount importance. Despite this, the mechanism of heme import by the ATP-binding-cassette (ABC) transporter HutCD in Vibrio cholerae remains unexplored. We have performed biochemical studies on ATPase HutD and its mutants, along with molecular modelling, docking and unbiased all-atom MD simulations on lipid-solvated models of permease-ATPase complex HutCD. The results demonstrated mechanisms of ATP binding/hydrolysis and trapped transient and global conformational changes in HutCD, necessary for heme internalization. ATPase HutD forms a dimer, independent of the permease HutC. Each HutD monomer canonically binds ATP in a 1:1 stoichiometry. MD simulations demonstrated that a rotational motion of HutC dimer occurs synchronously with the inter-dimeric D-loop interactions of HutDs. F151 of TM4-TM5 loop of HutC, packs with ATP and Y15 of HutD, initiating 'cytoplasmic gate opening' which mimics an 'outward-facing' to 'inward-facing' conformational switching upon ATP hydrolysis. The simulation on 'inward-facing' HutCD culminates to an 'occluded' state. The simulation on heme-docked HutCD indicated that the event of heme release occurs in ATP-free 'inward-facing' state. Gradual conformational changes of the TM5 helices of HutC towards the 'occluded' state facilitate ejection of heme.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2026-05-31T21:00:58.21Z","creation":"2025-04-04T21:43:43.131Z"},"accession":"S-EPMC9065009","cross_references":{"pubmed":["35504999"],"doi":["10.1038/s41598-022-11213-9"]}}