Uncovering of cytochrome P450 anatomy by SecStrAnnotator

Abstract

Protein structural families are groups of homologous proteins defined by the organization of secondary structure elements (SSEs). Nowadays, many families contain vast numbers of structures, and the SSEs can help to orient within them. Communities around specific protein families have even developed specialized SSE annotations, always assigning the same name to the equivalent SSEs in homologous proteins. A detailed analysis of the groups of equivalent SSEs provides an overview of the studied family and enriches the analysis of any particular protein at hand. We developed a workflow for the analysis of the secondary structure anatomy of a protein family. We applied this analysis to the model family of cytochromes P450 (CYPs)—a family of important biotransformation enzymes with a community-wide used SSE annotation. We report the occurrence, typical length and amino acid sequence for the equivalent SSE groups, the conservation/variability of these properties and relationship to the substrate recognition sites. We also suggest a generic residue numbering scheme for the CYP family. Comparing the bacterial and eukaryotic part of the family highlights the significant differences and reveals a well-known anomalous group of bacterial CYPs with some typically eukaryotic features. Our workflow for SSE annotation for CYP and other families can be freely used at address https://sestra.ncbr.muni.cz.

A Deep Dive into the Conformational Dynamics of CYP3A4 : Understanding the Binding of Homotropic and Non‐homotropic Ligands for Mitigating Drug‐Drug interaction (DDI)

“…Interestingly, in the present study we observed that these helices appeared to have RMSF values within 1–2 Å, whereas the region following helix F and G showed higher RMSF values in the range of 4–6 Å. This region include the residues 255 to 290 which corresponds to region helix H and the region preceding it [15,33] . The region between helix G and H (residue 255–270), showed RMSF values within 4–6 Å in the simulations of SysA, SysB and SysD.…”

Thetrans-zeatin-type side-chain modification of cytokinins controls rice growth

“…The cyp735a4-1 and cyp735a4-2 mutants are 263- and 298-base deletions, respectively. The 263- and 298-base deletions resulted in a predicted protein lacking “A helix”, a secondary structure conserved among cytochrome P450s (Midlik et al, 2021), and an in-frame stop codon at 4 codons after the mutation, respectively (Fig. S5).…”

Human Cytochrome P450 1, 2, 3 Families as Pharmacogenes with Emphases on Their Antimalarial and Antituberculosis Drugs and Prevalent African Alleles

“…The fold structure of CYP enzymes is largely conserved throughout the superfamily [ 37 , 46 ]. All known 3D structures of these proteins have a general shape that includes 14 helices and loops denoted A–L (A, B, Β′, C, D, E, F, G, H, I, J, K, K′, L) [ 23 ] ( Figure 1 A).…”

“…All known 3D structures of these proteins have a general shape that includes 14 helices and loops denoted A–L (A, B, Β′, C, D, E, F, G, H, I, J, K, K′, L) [ 23 ] ( Figure 1 A). Other helices such as A′, B″, F′, G′, J′, K″, and L′ have been observed to occur in the CYP structure at times [ 46 ]. CYPs also contain 4 β-sheets—β1 (5 strands), β2 (2 strands), β3 (3 strands), β4 (2 strands) in their structures, with two additional sheets, β5 and β6, occurring sometimes [ 23 , 46 ].…”

“…Other helices such as A′, B″, F′, G′, J′, K″, and L′ have been observed to occur in the CYP structure at times [ 46 ]. CYPs also contain 4 β-sheets—β1 (5 strands), β2 (2 strands), β3 (3 strands), β4 (2 strands) in their structures, with two additional sheets, β5 and β6, occurring sometimes [ 23 , 46 ]. Although the overall CYP structure is conserved, the size and shape of the active site can differ [ 43 ].…”