Vivoli, Mirella, Pang, Jiayun ORCID: 0000-0003-0689-8440 and Harmer, Nicholas J. (2017) A half-site multimeric enzyme achieves its cooperativity without conformational changes. Scientific Reports, 7 (1):16529. ISSN 2045-2322 (Print), 2045-2322 (Online) (doi:https://doi.org/10.1038/s41598-017-16421-2)

Preview

PDF (Publisher's PDF - Open Access) 18212 PANG_A_Half-Site_Multimeric_Enzyme_2017.pdf - Published Version Download (2MB) | Preview

Abstract

Cooperativity is a feature many multimeric proteins use to control activity. Here we show that the bacterial heptose isomerase GmhA displays homotropic positive and negative cooperativity among its four protomers. Most similar proteins achieve this through conformational changes: GmhA instead employs a delicate network of hydrogen bonds, and couples pairs of active sites controlled by a unique water channel. This network apparently raises the Lewis acidity of the catalytic zinc, thus increasing the activity at one active site at the cost of preventing substrate from adopting a reactive conformation at the paired negatively cooperative site – a “half-site” behavior. Our study establishes the principle that multimeric enzymes can exploit this cooperativity without conformational changes to maximize their catalytic power and control. More broadly, this subtlety by which enzymes regulate functions could be used to explore new inhibitor design strategies.

Item Type:	Article
Additional Information:	© The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Uncontrolled Keywords:	Computational models, Enzyme mechanisms, Active site cooperativity, zinc-dependent enzymes, Fukui indice
Subjects:	Q Science > QC Physics Q Science > QD Chemistry
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI) Faculty of Engineering & Science > Materials & Analysis Research Group
Last Modified:	21 Oct 2020 22:09
URI:	http://gala.gre.ac.uk/id/eprint/18212

Actions (login required)

View Item

Downloads