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Updated: Feb 20, 2026

Defining Substrate Specificities for Lipase and Phospholipase Candidates

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Published on: November 23, 2016

Substrate recognition by two different P450s: Evidence for conserved roles in a common fold.

Drew R Tietz¹, Allison M Colthart², Susan Sondej Pochapsky¹

¹Department of Chemistry, Brandeis University, MS 015, 415 South St, Waltham, MA, 02453, USA.

Scientific Reports

|October 21, 2017

Summary

Cytochrome P450 enzymes CYP101A1 and MycG bind substrates differently but undergo similar conformational changes. This suggests a shared mechanism for substrate recognition across the P450 enzyme superfamily.

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Identification of Kinase-substrate Pairs Using High Throughput Screening

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Published on: August 29, 2015

Area of Science:

Biochemistry
Enzymology
Structural Biology

Background:

Cytochrome P450 enzymes are crucial for diverse biological oxidations.
CYP101A1 and MycG are P450 enzymes with distinct substrates and low sequence homology.
Understanding substrate binding mechanisms is key to enzyme function.

Purpose of the Study:

To investigate and compare the substrate-induced conformational changes in CYP101A1 and MycG.
To identify similarities in substrate binding mechanisms despite differing enzyme structures and substrates.
To explore potential common recognition mechanisms within the P450 superfamily.

Main Methods:

Solution Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study enzyme conformational changes.
Comparative analysis of structural perturbations upon substrate binding in both enzymes.

Main Results:

Both CYP101A1 and MycG exhibited significant conformational changes upon binding their respective substrates (d-camphor and mycinamicin IV).
Despite low sequence identity (29%) and different substrate properties, similar secondary structural features were perturbed in both enzymes.
These perturbations indicate a conserved response to substrate engagement.

Conclusions:

A common mechanism for substrate binding and recognition likely exists within the Cytochrome P450 superfamily.
Conformational flexibility plays a significant role in P450 substrate interactions.
NMR studies provide valuable insights into the conserved functional mechanisms of P450 enzymes.