dc.contributor.author | Vivoli, M | |
dc.contributor.author | Pang, J | |
dc.contributor.author | Harmer, NJ | |
dc.date.accessioned | 2018-01-10T15:34:29Z | |
dc.date.issued | 2017-11-28 | |
dc.description.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. | en_GB |
dc.description.sponsorship | This work was funded by grants from the Royal Society (2009/R2) and BBSRC (BB/H019685/1) to NH. | en_GB |
dc.identifier.citation | Vol. 7, article 16529 | en_GB |
dc.identifier.doi | 10.1038/s41598-017-16421-2 | |
dc.identifier.uri | http://hdl.handle.net/10871/30898 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Nature | en_GB |
dc.rights | © Te 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/. | en_GB |
dc.subject | Computational models | en_GB |
dc.subject | Enzyme mechanisms | en_GB |
dc.title | A half-site multimeric enzyme achieves its cooperativity without conformational changes | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-01-10T15:34:29Z | |
dc.identifier.issn | 2045-2322 | |
dc.description | This is the final version of the article. Available from Springer Nature via the DOI in this record. | en_GB |
dc.identifier.journal | Scientific Reports | en_GB |