Probing protein structures in solution by molecular dynamics simulation and small-angle x-ray scattering

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dc.contributor.authorYang, HCen_AU
dc.contributor.authorLin, SWen_AU
dc.contributor.authorGe, YCen_AU
dc.contributor.authorHuang, MYen_AU
dc.contributor.authorYang, CHen_AU
dc.contributor.authorLiu, WMen_AU
dc.contributor.authorDuff, APen_AU
dc.contributor.authorWu, CMen_AU
dc.contributor.authorLan, YKen_AU
dc.contributor.authorSu, ACen_AU
dc.contributor.authorYeh, YQen_AU
dc.contributor.authorJeng, USen_AU
dc.contributor.authorChou, PTen_AU
dc.date.accessioned2024-02-23T00:47:38Zen_AU
dc.date.available2024-02-23T00:47:38Zen_AU
dc.date.issued2021-08-14en_AU
dc.date.statistics2023-04-20en_AU
dc.description.abstractLore of chemical biology guides us that drug discovery of protein binding relies on either optimize the active site complexity of lock and key or induced-fit with conformation selection dynamics; yet, the latter that often-coupled protein interior transport dynamics was much harder to study due to its lack of strong interactions in transient states.[1-2] This study starts to make progress in using in-situ operando X-ray and neutron contrast variation techniques to depict the landscape of protein binding substrate dynamics in solution. We herein demonstrate, for the first time, the 3-D dynamical structures of hydrated CYP450 protein exterior surfaces to interior buried heme site by a distributed connection of channels that direct the reactant in and out. Using CYP450s of prostacyclin synthase (PGIS) and thromboxane synthase (TXAS) as prototypes we have unveiled the unique dynamics of P450 functional channels in/out the haem site, which drive a variety of water molecules motion, water density change and pre-organization toward the heme active site and hence harness the substrate binding selectivity. The result is able to clarify how these two proteins catalyze the same substrate of prostaglandin H2 by entirely different regio-chemical-selective pathways. © The Authorsen_AU
dc.description.sponsorshipThis work was supported by grants from the Ministry of Science and Technology of Taiwan (Grant Nos. MOST 109-2113-M-030-002).en_AU
dc.identifier.citationYang, H.-C., Lin, S.-W., Ge, Y.-C., Huang, M.-Y., Yang, C.-H., Liu, W.-M., Duff, A. P., Wu, C.-M., Lan, Y.-K., Su, A.-C., Yeh, Y.-Q., Jeng, U.-S., & Chou, P.-T. (2021). Probing protein structures in solution by molecular dynamics simulation and small-angle x-ray scattering. Poster presented to the IUCr 2021, 25th Congress of the International Union of Crystallography, 14-22 August 2021, Prague, Czech Republic. In Acta Crystallographica Section A, 77(a2), C704. doi:10.1107/S0108767321089923en_AU
dc.identifier.conferenceenddate2021-08-22en_AU
dc.identifier.conferencenameIUCr 2021, 25th Congress of the International Union of Crystallographyen_AU
dc.identifier.conferenceplacePrague, Czech Republicen_AU
dc.identifier.conferencestartdate2021-08-14en_AU
dc.identifier.issn2053-2733en_AU
dc.identifier.issuea2en_AU
dc.identifier.journaltitleActa Crystallographica Section A : Foundations and Advancesen_AU
dc.identifier.otherPS-1-17en_AU
dc.identifier.paginationC704en_AU
dc.identifier.urihttps://doi.org/doi:10.1107/S0108767321089923en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15408en_AU
dc.identifier.volume77en_AU
dc.language.isoenen_AU
dc.publisherInternational Union of Crystallographyen_AU
dc.subjectProteinsen_AU
dc.subjectSmall angle scatteringen_AU
dc.subjectCytochromesen_AU
dc.subjectSubstratesen_AU
dc.subjectMolecular dynamics methoden_AU
dc.subjectWateren_AU
dc.subjectMoloculesen_AU
dc.titleProbing protein structures in solution by molecular dynamics simulation and small-angle x-ray scatteringen_AU
dc.typeConference Posteren_AU
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