دورية أكاديمية
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Deacylation Mechanism by SIRT2 Revealed in the 1'-SH-2'-O-Myristoyl Intermediate Structure.

التفاصيل البيبلوغرافية
العنوان: Deacylation Mechanism by SIRT2 Revealed in the 1'-SH-2'-O-Myristoyl Intermediate Structure.
المؤلفون: Wang Y; School of Biomedical Sciences, University of Hong Kong, Hong Kong, China., Fung YME; State Key Laboratory of Synthetic Chemistry and Department of Chemistry, University of Hong Kong, Hong Kong, China., Zhang W; School of Biomedical Sciences, University of Hong Kong, Hong Kong, China; Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China., He B; College of Pharmacy, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM Ministry of Education, Guizhou Medical University, Guizhou 550004, China., Chung MWH; School of Biomedical Sciences, University of Hong Kong, Hong Kong, China., Jin J; School of Biomedical Sciences, University of Hong Kong, Hong Kong, China., Hu J; Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Cornell University, Ithaca, NY 14853, USA., Lin H; Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Cornell University, Ithaca, NY 14853, USA. Electronic address: hl379@cornell.edu., Hao Q; School of Biomedical Sciences, University of Hong Kong, Hong Kong, China. Electronic address: qhao@hku.hk.
المصدر: Cell chemical biology [Cell Chem Biol] 2017 Mar 16; Vol. 24 (3), pp. 339-345. Date of Electronic Publication: 2017 Mar 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101676030 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2451-9448 (Electronic) Linking ISSN: 24519448 NLM ISO Abbreviation: Cell Chem Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, MA : Cell Press, 2016-
مواضيع طبية MeSH: Fatty Acids, Monounsaturated/*chemistry , Sirtuin 2/*metabolism, Acylation ; Biocatalysis ; Crystallography, X-Ray ; Humans ; NAD/analogs & derivatives ; NAD/chemistry ; NAD/metabolism ; Peptides/analysis ; Peptides/chemical synthesis ; Peptides/metabolism ; Protein Structure, Tertiary ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/chemistry ; Recombinant Proteins/isolation & purification ; Sirtuin 2/chemistry ; Sirtuin 2/genetics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
مستخلص: Sirtuins are NAD-dependent deacylases. Previous studies have established two important enzymatic intermediates in sirtuin-catalyzed deacylation, an alkylamidate intermediate I, which is then converted to a bicyclic intermediate II. However, how intermediate II is converted to products is unknown. Based on potent SIRT2-specific inhibitors we developed, here we report crystal structures of SIRT2 in complexes with a thiomyristoyl lysine peptide-based inhibitor and carba-NAD or NAD. Interestingly, by soaking crystals with NAD, we capture a distinct covalent catalytic intermediate (III) that is different from the previously established intermediates I and II. In this intermediate, the covalent bond between the S and the myristoyl carbonyl carbon is broken, and we believe this intermediate III to be the decomposition product of II en route to form the end products. MALDI-TOF data further support the intermediate III formation. This is the first time such an intermediate has been captured by X-ray crystallography and provides more mechanistic insights into sirtuin-catalyzed reactions.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
التعليقات: Comment in: Cell Chem Biol. 2017 Mar 16;24(3):248-249. (PMID: 28306500)
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معلومات مُعتمدة: R01 GM098596 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: crystallography; enzyme; post-translational modifications; reactive intermediates; sirtuins
المشرفين على المادة: 0 (Fatty Acids, Monounsaturated)
0 (Peptides)
0 (Recombinant Proteins)
0U46U6E8UK (NAD)
112345-60-5 (carbanicotinamide adenine dinucleotide)
EC 3.5.1.- (Sirtuin 2)
RF23WGD123 (9-tetradecenoic acid)
تواريخ الأحداث: Date Created: 20170314 Date Completed: 20171121 Latest Revision: 20181113
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC5365152
DOI: 10.1016/j.chembiol.2017.02.007
PMID: 28286128
قاعدة البيانات: MEDLINE
الوصف
تدمد:2451-9448
DOI:10.1016/j.chembiol.2017.02.007