Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Computational insights into the different catalytic activities of CYP3A4 and CYP3A5 toward schisantherin E
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology.
Show others and affiliations
2019 (English)In: Chemical Biology and Drug Design, ISSN 1747-0277, E-ISSN 1747-0285, Vol. 93, no 5, p. 854-864Article in journal (Refereed) Published
Abstract [en]

The cytochromes CYP3A4 and CYP3A5 share 84% sequence identity, but they exhibit different catalytic activities toward some substrates. Schisantherin E (SE) was recently identified as a selective substrate of CYP3A5, which exhibited catalytic efficiency that was more than 23 times higher than CYP3A4. At present, however, the structural determinants responsible for the different catalytic activities of the two enzymes toward SE have not been fully understood. In this study, a combination of molecular docking, molecular dynamic simulations, and binding free energy calculation was performed on the CYP3A4/CYP3A5-SE systems to investigate the issue. The results demonstrate that Ser119 in CYP3A4 and Glu374 in CYP3A5 formed direct hydrogen bonding with SE, respectively. Additionally, one water molecule located between the B-C loop and the I helix mediated different hydrogen-bonding networks between CYP3A4/3A5 and SE. The residue differences (Phe/Leu108 and Leu/Phe210) triggered the distinct conformational changes of the Phe-cluster residues, especially Phe213 and Phe215, which formed stronger hydrophobic interactions with SE in CYP3A5. The calculated binding free energies were consistent with the experimental results.

Place, publisher, year, edition, pages
Blackwell Publishing, 2019. Vol. 93, no 5, p. 854-864
National Category
Theoretical Chemistry
Identifiers
URN: urn:nbn:se:kth:diva-252984DOI: 10.1111/cbdd.13475ISI: 000468814500015PubMedID: 30637977Scopus ID: 2-s2.0-85061042891OAI: oai:DiVA.org:kth-252984DiVA, id: diva2:1342797
Note

QC 20190814

Available from: 2019-08-14 Created: 2019-08-14 Last updated: 2019-08-14Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records BETA

Li, Junhao

Search in DiVA

By author/editor
Li, Junhao
By organisation
Theoretical Chemistry and Biology
In the same journal
Chemical Biology and Drug Design
Theoretical Chemistry

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 3 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf