Comparative Analysis, Structural Insights, and Substrate/Drug Interaction of CYP128A1 in

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Jul 12

PMID 32650369

Citations 6

Authors

Nokwanda Samantha Ngcobo

Zinhle Edith Chiliza

Wanping Chen

Jae-Hyuk Yu

David R Nelson

Jack A Tuszynski

Jordane Preto

Khajamohiddin Syed

Affiliations

Soon will be listed here.

Abstract

Cytochrome P450 monooxygenases (CYPs/P450s) are well known for their role in organisms' primary and secondary metabolism. Among 20 P450s of the tuberculosis-causing H37Rv, CYP128A1 is particularly important owing to its involvement in synthesizing electron transport molecules such as menaquinone-9 (MK9). This study employs different approaches to understand CYP128 P450 family's distribution and structural aspects. Genome data-mining of 4250 mycobacterial species has revealed the presence of 2674 P450s in 2646 mycobacterial species belonging to six different categories. Contrast features were observed in the gene distribution, subfamily patterns, and characteristics of the secondary metabolite biosynthetic gene cluster (BGCs) between (MTBC) and other mycobacterial category species. In all MTBC species (except one) CYP128 P450s belong to subfamily A, whereas subfamily B is predominant in another four mycobacterial category species. Of CYP128 P450s, 78% was a part of BGCs with , or together with and . The CYP128 family ranked fifth in the conservation ranking. Unique amino acid patterns are present at the EXXR and CXG motifs. Molecular dynamic simulation studies indicate that the CYP128A1 bind to MK9 with the highest affinity compared to the azole drugs analyzed. This study provides comprehensive comparative analysis and structural insights of CYP128A1 in .

Citing Articles

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