The binding of nitrogen-donor ligands to the ferric and ferrous forms of cytochrome P450 enzymes

Mohamed, Hebatalla; Ghith, Amna; Bell, Stephen

doi:10.1016/j.jinorgbio.2023.112168

Cited by 5 publications

(1 citation statement)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To probe the importance of this interaction for catalysis, a H234L P450 Blt mutant was generated and the binding and turnover of the MRYLH substrate explored (Table , Figure ). The importance of His-234 for catalysis was confirmed by an order of magnitude reduction in cross-linking demonstrated by the H234L mutant (>9% vs 85% for WT), and can be explained by the altered binding mode seen with this mutant, which switches to an inhibition-type spectrum that is explicable either via direct or water-mediated His-coordination to the haem of P450 Blt due to the loss of the interaction with His-234 . The marked effect of the H234L mutation is in contrast with the more minor effects of mutating the major nonpolar I-helix residue that interacts with the side chains of the MRYLH peptide (Ala-231) in an A231 V mutant (53% conversion), showing the importance of His-234 for both binding and turnover of the MRYLH substrate.…”

Section: Results and Discussionmentioning

confidence: 99%

Structural Insights into a Side Chain Cross-Linking Biarylitide P450 from RiPP Biosynthesis

Hansen,

Keto,

Treisman

et al. 2024

ACS Catal.

View full text Add to dashboard Cite

Peptide side chain cross-linking is an important feature of many natural products, with an increasing number of examples catalyzed by cytochrome P450s being reported from ribosomal biosynthesis pathways in addition to well-known examples from nonribosomal peptide antibiotics. Despite the dramatic recent increase in the number of enzymes and reactions catalyzed, substrate bound structures of such P450s have proven elusive to date. Here, we report the structural characterization of the biarylitide cross-linking enzyme P450 Blt in complex with its pentapeptide substrate MRYLH. This structure, in combination with computational and biochemical experiments, shows the importance of key I-helix residues in this P450 in coordinating to the histidine residue of the substrate and further that this appears to be central to the specificity of this enzyme for generating a C−N link between the tyrosine and histidine residues in the MRYLH substrate. The structure of the P450 Blt -MRYLH complex provides the first insight into how peptide substrates can be accommodated within P450s and offers insights into how other examples of related P450s can accept the varied substrates that have recently been identified using bioinformatic methods.

show abstract

Section: Results and Discussionmentioning

confidence: 99%