{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Blachly PG"],"funding":["Howard Hughes Medical Institute","NIGMS NIH HHS","PHS HHS"],"pagination":["e1003395"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3868525"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(12)"],"pubmed_abstract":["The nonmevalonate pathway is responsible for isoprenoid production in microbes, including H. pylori, M. tuberculosis and P. falciparum, but is nonexistent in humans, thus providing a desirable route for antibacterial and antimalarial drug discovery. We coordinate a structural study of IspH, a [4Fe-4S] protein responsible for converting HMBPP to IPP and DMAPP in the ultimate step in the nonmevalonate pathway. By performing accelerated molecular dynamics simulations on both substrate-free and HMBPP-bound [Fe4S4](2+) IspH, we elucidate how substrate binding alters the dynamics of the protein. Using principal component analysis, we note that while substrate-free IspH samples various open and closed conformations, the closed conformation observed experimentally for HMBPP-bound IspH is inaccessi"],"journal":["PLoS computational biology"],"pubmed_title":["Utilizing a dynamical description of IspH to aid in the development of novel antimicrobial drugs."],"pmcid":["PMC3868525"],"funding_grant_id":["NIHGM31749","T32 GM008326"],"pubmed_authors":["Blachly PG","McCammon JA","Williams SL","de Oliveira CA"],"additional_accession":[]},"is_claimable":false,"name":"Utilizing a dynamical description of IspH to aid in the development of novel antimicrobial drugs.","description":"The nonmevalonate pathway is responsible for isoprenoid production in microbes, including H. pylori, M. tuberculosis and P. falciparum, but is nonexistent in humans, thus providing a desirable route for antibacterial and antimalarial drug discovery. We coordinate a structural study of IspH, a [4Fe-4S] protein responsible for converting HMBPP to IPP and DMAPP in the ultimate step in the nonmevalonate pathway. By performing accelerated molecular dynamics simulations on both substrate-free and HMBPP-bound [Fe4S4](2+) IspH, we elucidate how substrate binding alters the dynamics of the protein. Using principal component analysis, we note that while substrate-free IspH samples various open and closed conformations, the closed conformation observed experimentally for HMBPP-bound IspH is inaccessi","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013","modification":"2026-04-14T17:16:03.174Z","creation":"2019-03-27T01:18:45Z"},"accession":"S-EPMC3868525","cross_references":{"pubmed":["24367248"],"doi":["10.1371/journal.pcbi.1003395"]}}