Friends and relatives : insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN
(2024) In Faraday Discussions 252. p.341-353- Abstract
Noncovalent interaction networks provide a powerful means to represent and analyze protein structure. Such networks can represent both static structures and dynamic conformational ensembles. We have recently developed two tools for analyzing such interaction networks and generating hypotheses for protein engineering. Here, we apply these tools to the conformational regulation of substrate specificity in class A β-lactamases, particularly the evolutionary development from generalist to specialist catalytic function and how that can be recapitulated or reversed by protein engineering. These tools, KIF and KIN, generate a set of prioritized residues and interactions as targets for experimental protein engineering.
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/9ab192db-8804-4b8a-87f3-4c080a003f76
- author
- Yehorova, Dariia ; Crean, Rory M ; Kasson, Peter M and Kamerlin, Shina Caroline Lynn
- publishing date
- 2024-09-11
- type
- Contribution to journal
- publication status
- published
- keywords
- Protein Conformation, beta-Lactamases/chemistry, Evolution, Molecular, Protein Engineering, Substrate Specificity, Models, Molecular
- in
- Faraday Discussions
- volume
- 252
- pages
- 13 pages
- publisher
- Royal Society of Chemistry
- external identifiers
-
- pmid:38842247
- scopus:85195392889
- ISSN
- 1359-6640
- DOI
- 10.1039/d4fd00018h
- language
- English
- LU publication?
- no
- id
- 9ab192db-8804-4b8a-87f3-4c080a003f76
- date added to LUP
- 2025-01-11 18:18:01
- date last changed
- 2025-07-13 18:37:25
@article{9ab192db-8804-4b8a-87f3-4c080a003f76, abstract = {{<p>Noncovalent interaction networks provide a powerful means to represent and analyze protein structure. Such networks can represent both static structures and dynamic conformational ensembles. We have recently developed two tools for analyzing such interaction networks and generating hypotheses for protein engineering. Here, we apply these tools to the conformational regulation of substrate specificity in class A β-lactamases, particularly the evolutionary development from generalist to specialist catalytic function and how that can be recapitulated or reversed by protein engineering. These tools, KIF and KIN, generate a set of prioritized residues and interactions as targets for experimental protein engineering.</p>}}, author = {{Yehorova, Dariia and Crean, Rory M and Kasson, Peter M and Kamerlin, Shina Caroline Lynn}}, issn = {{1359-6640}}, keywords = {{Protein Conformation; beta-Lactamases/chemistry; Evolution, Molecular; Protein Engineering; Substrate Specificity; Models, Molecular}}, language = {{eng}}, month = {{09}}, pages = {{341--353}}, publisher = {{Royal Society of Chemistry}}, series = {{Faraday Discussions}}, title = {{Friends and relatives : insight into conformational regulation from orthologues and evolutionary lineages using KIF and KIN}}, url = {{http://dx.doi.org/10.1039/d4fd00018h}}, doi = {{10.1039/d4fd00018h}}, volume = {{252}}, year = {{2024}}, }