Differences in nucleotide specificity and catalytic mechanism between Vibrio harveyi aldehyde dehydrogenase and other members of the aldehyde dehydrogenase superfamily |
| |
| Institution: | 1. Instituto Politécnico Nacional, Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA) Unidad Legaria, Legaria 694, Colonia Irrigación, Delegación Miguel Hidalgo, Ciudad de México 11500, Mexico;2. CONACyT, Instituto Politécnico Nacional, Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA) Unidad Legaria, Legaria 694, Colonia Irrigación, Delegación Miguel Hidalgo, Ciudad de México 11500, Mexico;3. Gleb Wataghin Physics Institute, University of Campinas – UNICAMP, 13083-859 Campinas, SP, Brazil;3. Departments of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106-4965;4. Departments of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4965;5. Center for Proteomics and Bioinformatics, Center for Synchrotron Biosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4988;1. Center of Research and Development on Life Sciences and Environment Sciences, Harbin University of Commerce, Harbin 150076, China;2. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China;3. Institute of Medicine Plantationof Chongqing, Chongqing 408435, China;4. College of chemistry and materials science, Guangxi Teachers Education University, Manning 530001, China;1. Cell Culture Laboratory, Postgraduate Program in Biotechnology, Centro Universitário UNIVATES, Av. Avelino Tallini, 171, CEP: 959000-000 Lajeado, Rio Grande do Sul, Brazil;2. Cellular and Molecular Laboratory, Medical School, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil;3. Center for Biological and Health Sciences, Centro Universitário UNIVATES, Av. Avelino Tallini, 171, CEP: 95900-000, Lajeado, RS, Brazil |
| |
| Abstract: | The fatty aldehyde dehydrogenase (Vh-ALDH) isolated from the luminescent bacterium, Vibrio harveyi, differs from other aldehyde dehydrogenases in its high affinity for NADP+. The binding of NADP+ appears to arise from the interaction of the 2′-phosphate of the adenosine moiety of NADP+ with a threonine (T175) in the nucleotide recognition site just after the βB strand as well as with an arginine (R210) that pi stacks over the adenosine moiety. The active site of Vh-ALDH contains the usual suspects of a cysteine (C289), two glutamates (E253 and E377) and an asparagine (N147) involved in the aldehyde dehydrogenase mechanism. However, Vh-ALDH has one polar residue in the active site that distinguishes it from other ALDHs; a histidine (H450) is in close contact with the cysteine nucleophile. As a glutamate has been implicated in promoting the nucleophilicity of the active site cysteine residue in ALDHs, the close contact of a histidine with the cysteine nucleophile in Vh-ALDH raises the possibility of alternate routes to increase the reactivity of the cysteine nucleophile. The effects of mutation of these residues on the different functions catalyzed by Vh-ALDH including acylation, (thio)esterase, reductase and dehydrogenase activities should help define the specific roles of the residues in the active site of ALDHs. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
