hydrophobic cluster
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2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yuxin Ye ◽  
Yuxian Xiong ◽  
Hao Huang

AbstractIpaH enzymes are bacterial E3 ligases targeting host proteins for ubiquitylation. Two autoinhibition modes of IpaH enzymes have been proposed based on the relative positioning of the Leucine-rich repeat domain (LRR) with respect to the NEL domain. In mode 1, substrate-binding competitively displaces the interactions between theLRR and NEL to relieve autoinhibition. However, the molecular basis for mode 2 is unclear. Here, we present the crystal structures of Shigella IpaH9.8 and the LRR of IpaH9.8 in complex with the substrate of human guanylate-binding protein 1 (hGBP1). A hydrophobic cluster in the C-terminus of IpaH9.8LRR forms a hydrophobic pocket involved in binding the NEL domain, and the binding is important for IpaH9.8 autoinhibition. Substrate-binding destabilizes the hydrophobic cluster by inducing conformational changes of IpaH9.8LRR. Arg166 and Phe187 in IpaH9.8LRR function as sensors for substrate-binding. Collectively, our findings provide insights into the molecular mechanisms for the actication of IpaH9.8 in autoinhibition mode 2.



Biochimie ◽  
2019 ◽  
Vol 167 ◽  
pp. 68-80 ◽  
Author(s):  
Alexis Lamiable ◽  
Tristan Bitard-Feildel ◽  
Joseph Rebehmed ◽  
Flavien Quintus ◽  
Françoise Schoentgen ◽  
...  


PROTEOMICS ◽  
2018 ◽  
Vol 18 (21-22) ◽  
pp. 1800054 ◽  
Author(s):  
Tristan Bitard-Feildel ◽  
Alexis Lamiable ◽  
Jean-Paul Mornon ◽  
Isabelle Callebaut


2018 ◽  
Author(s):  
Tristan Bitard-Feildel ◽  
Isabelle Callebaut

AbstractMotivation: Detecting protein domains sharing no similarity to known domains, as stored in domain databases, is a challenging problem, particularly for unannotated proteomes, domains emerged recently, fast diverging proteins or domains with intrinsically disordered regions.Results: We developed pyHCA and HCAtk, a python API and standalone tool gathering together improved versions of previously developed methodologies, with new functionalities. The developed tools can be either used from command line or from a python API.Availability: HCAtk and pyHCA are available at https://github.com/T-B-F/pyHCA under the CeCILL-C license.



2017 ◽  
Vol 1859 (2) ◽  
pp. 135-145 ◽  
Author(s):  
Scott M. Gordon ◽  
Mohsen Pourmousa ◽  
Maureen Sampson ◽  
Denis Sviridov ◽  
Rafique Islam ◽  
...  


2016 ◽  
Vol 83 (2) ◽  
Author(s):  
Taisuke Wakamatsu ◽  
Haruhiko Sakuraba ◽  
Megumi Kitamura ◽  
Yuichi Hakumai ◽  
Kenji Fukui ◽  
...  

ABSTRACT l-Tryptophan dehydrogenase from Nostoc punctiforme NIES-2108 (NpTrpDH), despite exhibiting high amino acid sequence identity (>30%)/homology (>50%) with NAD(P)+-dependent l-Glu/l-Leu/l-Phe/l-Val dehydrogenases, exclusively catalyzes reversible oxidative deamination of l-Trp to 3-indolepyruvate in the presence of NAD+. Here, we determined the crystal structure of the apo form of NpTrpDH. The structure of the NpTrpDH monomer, which exhibited high similarity to that of l-Glu/l-Leu/l-Phe dehydrogenases, consisted of a substrate-binding domain (domain I, residues 3 to 133 and 328 to 343) and an NAD+/NADH-binding domain (domain II, residues 142 to 327) separated by a deep cleft. The apo-NpTrpDH existed in an open conformation, where domains I and II were apart from each other. The subunits dimerized themselves mainly through interactions between amino acid residues around the β-1 strand of each subunit, as was observed in the case of l-Phe dehydrogenase. The binding site for the substrate l-Trp was predicted by a molecular docking simulation and validated by site-directed mutagenesis. Several hydrophobic residues, which were located in the active site of NpTrpDH and possibly interacted with the side chain of the substrate l-Trp, were arranged similarly to that found in l-Leu/l-Phe dehydrogenases but fairly different from that of an l-Glu dehydrogenase. Our crystal structure revealed that Met-40, Ala-69, Ile-74, Ile-110, Leu-288, Ile-289, and Tyr-292 formed a hydrophobic cluster around the active site. The results of the site-directed mutagenesis experiments suggested that the hydrophobic cluster plays critical roles in protein folding, l-Trp recognition, and catalysis. Our results provide critical information for further characterization and engineering of this enzyme. IMPORTANCE In this study, we determined the three-dimensional structure of l-Trp dehydrogenase, analyzed its various site-directed substitution mutants at residues located in the active site, and obtained the following informative results. Several residues in the active site form a hydrophobic cluster, which may be a part of the hydrophobic core essential for protein folding. To our knowledge, there is no previous report demonstrating that a hydrophobic cluster in the active site of any l-amino acid dehydrogenase may have a critical impact on protein folding. Furthermore, our results suggest that this hydrophobic cluster could strictly accommodate l-Trp. These studies show the structural characteristics of l-Trp dehydrogenase and hence would facilitate novel applications of l-Trp dehydrogenase.



2016 ◽  
Vol 6 (4) ◽  
pp. 317-319 ◽  
Author(s):  
Olga A. Kolosova ◽  
Konstantin S. Usachev ◽  
Albert V. Aganov ◽  
Vladimir V. Klochkov


Biochimie ◽  
2015 ◽  
Vol 119 ◽  
pp. 244-253 ◽  
Author(s):  
Tristan Bitard-Feildel ◽  
Magdalena Heberlein ◽  
Erich Bornberg-Bauer ◽  
Isabelle Callebaut


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