Sökning: WFRF:(Tu Yaoquan) > Homotropic Cooperat...
Fältnamn | Indikatorer | Metadata |
---|---|---|
000 | 03194naa a2200373 4500 | |
001 | oai:DiVA.org:kth-298171 | |
003 | SwePub | |
008 | 210629s2021 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-2981712 URI |
024 | 7 | a https://doi.org/10.1021/acs.jcim.1c002662 DOI |
040 | a (SwePub)kth | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Li, Junhaou KTH,Teoretisk kemi och biologi4 aut0 (Swepub:kth)u1wxbd82 |
245 | 1 0 | a Homotropic Cooperativity of Midazolam Metabolism by Cytochrome P450 3A4 :b Insight from Computational Studies |
264 | c 2021-04-22 | |
264 | 1 | b American Chemical Society (ACS),c 2021 |
338 | a print2 rdacarrier | |
500 | a QC 20210629 | |
520 | a Human cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of similar to 50% clinically used drugs. Midazolam (MDZ) is a commonly used sedative drug and serves as a marker substrate for the CYP3A4 activity assessment. MDZ is metabolized by CYP3A4 to two hydroxylation products, 1'-OH-MDZ and 4-OH-MDZ. It has been reported that the ratio of 1'-OH-MDZ and 4-OH-MDZ is dependent on the MDZ concentration, which reflects the homotropic cooperative behavior in MDZ metabolism by CYP3A4. Here, we used quantum chemistry (QC), molecular docking, conventional molecular dynamics (cMD), and Gaussian accelerated molecular dynamics (GaMD) approaches to investigate the mechanism of the interactions between CYP3A4 and MDZ. QC calculations suggest that C1' is less reactive for hydroxylation than C4, which is a pro-chirality carbon. However, the 4-OH-MDZ product is likely to be racemic due to the chirality inversion in the rebound step. The MD simulation results indicate that MDZ at the peripheral allosteric site is not stable and the binding modes of the MDZ molecules at the productive site are in line with the experimental observations. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng |
700 | 1 | a Chen, Yueu East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China.4 aut |
700 | 1 | a Tang, Yunu East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China.4 aut |
700 | 1 | a Li, Weihuau East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China.4 aut |
700 | 1 | a Tu, Yaoquanu KTH,Teoretisk kemi och biologi4 aut0 (Swepub:kth)u1kuh2ie |
710 | 2 | a KTHb Teoretisk kemi och biologi4 org |
773 | 0 | t Journal of Chemical Information and Modelingd : American Chemical Society (ACS)g 61:5, s. 2418-2426q 61:5<2418-2426x 1549-9596x 1549-960X |
856 | 4 | u https://doi.org/10.1021/acs.jcim.1c00266y Fulltext |
856 | 4 | u https://pubs.acs.org/doi/pdf/10.1021/acs.jcim.1c00266 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-298171 |
856 | 4 8 | u https://doi.org/10.1021/acs.jcim.1c00266 |
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
Kopiera och spara länken för att återkomma till aktuell vy