Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox
Authors: Mikael Elias
Eric Chabriere
Julien Hiblot
Guillaume Gotthard
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Enzymes; Catalysts; Conformational states; Active site; Lactonase
Affiliations: URMITE UMR CNRS-IRD 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France.

Abstract:  Enzymes are proficient catalysts that enable fast rates of Michaelis-complex formation, the chemical step and products release. These different steps may require different conformational states of the active site that have distinct binding properties. Moreover, the conformational flexibility of the active site mediates alternative, promiscuous functions. Here we focused on the lactonase SsoPox from Sulfolobus solfataricus. SsoPox is a native lactonase endowed with promiscuous phosphotriesterase activity. We identified a position in the active site loop (W263) that governs its flexibility, and thereby affects the substrate specificity of the enzyme. We isolated two different sets of substitutions at position 263 that induce two distinct conformational sampling of the active loop and characterized the structural and kinetic effects of these substitutions. These sets of mutations selectively and distinctly mediate the improvement of the promiscuous phosphotriesterase and oxo-lactonase activities of SsoPox by increasing active-site loop flexibility. These observations corroborate the idea that conformational diversity governs enzymatic promiscuity and is a key feature of protein evolvability. 

Retracted: No

PubPeer comments:
 After reaching to the journal, authors decided to publish this comment to address the incorrectly filed Competing Interests Statement: https: journals.plos.org plosone article comment?id=10.1371 annotation d144574d-2f55-4201-b3e2-81665833f21f ![file] , 
 Thank you Dr Elias for this correction, but I would like to highlight a fact: This article is cited on the bibliography page of the website of Gene Green Tk: https: www.gene-greentk.com bibliography On the website of this company, we can see that you, as well as the last author are founders of this company https: www.gene-greentk.com team Thus, one could think the **potential conflict of interest should also be disclosed**. , 
 Dear Reader, This disclosure appears sufficient. The company is also citing papers dating back many years prior its creation on the website. Citing relevant literature on the website is not a point here. This paper was actually submitted to the journal before the company was created, let alone the research done. Thank you. , 
 Therefore, for this obvious reason, there are no COI with the startup company. , 
 I would like to clarify. The bibliography section of the startup company (that I do not edit) lists papers that can illustrate the topic or the expertise of the team. This is why older papers can be found. It is not a list of papers with COI. What determines a potential COI is the content of the paper. I have disclosed elsewhere that concomitantly to the discussions with Dr. Bik, my papers and COI were fully reviewed at my institution. Disclosures are satisfactory, and a COI management plan is in place. ,