دورية أكاديمية
Deacylation Mechanism by SIRT2 Revealed in the 1'-SH-2'-O-Myristoyl Intermediate Structure.
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) |
References: | Structure. 2006 Aug;14(8):1231-40. (PMID: 16905097) Curr Opin Chem Biol. 2012 Dec;16(5-6):535-43. (PMID: 23102634) J Biol Chem. 2007 Oct 12;282(41):30239-45. (PMID: 17684016) J Biol Chem. 2005 Mar 18;280(11):10264-76. (PMID: 15632193) Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):E2772-81. (PMID: 23840057) Science. 2011 Nov 11;334(6057):806-9. (PMID: 22076378) Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10042-7. (PMID: 15220471) J Biol Chem. 2013 Oct 25;288(43):31350-6. (PMID: 24052263) Cancer Cell. 2016 May 9;29(5):767-768. (PMID: 27165747) J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840) Cell. 2004 Feb 20;116(4):551-63. (PMID: 14980222) Biochemistry. 2001 Dec 25;40(51):15456-63. (PMID: 11747420) Elife. 2014 Nov 04;3:null. (PMID: 25369635) Nature. 2000 Feb 17;403(6771):795-800. (PMID: 10693811) Mol Cell. 2007 Feb 9;25(3):463-72. (PMID: 17289592) J Am Chem Soc. 2016 Sep 28;138(38):12304-7. (PMID: 27610633) J Biol Chem. 2012 Aug 17;287(34):28307-14. (PMID: 22767592) J Biol Chem. 2013 Oct 11;288(41):29252-9. (PMID: 23974119) Structure. 2008 Sep 10;16(9):1368-77. (PMID: 18786399) Science. 2002 Dec 20;298(5602):2390-2. (PMID: 12493915) Acta Crystallogr D Biol Crystallogr. 1994 Mar 1;50(Pt 2):139-54. (PMID: 15299452) Cell. 2014 Dec 18;159(7):1615-25. (PMID: 25525879) J Biol Chem. 2007 Dec 21;282(51):37256-65. (PMID: 17951578) Methods Enzymol. 1997;276:307-26. (PMID: 27754618) Angew Chem Int Ed Engl. 2015 Jan 19;54(4):1149-52. (PMID: 25476551) Clin Epigenetics. 2013 Jul 19;5(1):11. (PMID: 23870485) J Org Chem. 2012 Sep 7;77(17):7319-29. (PMID: 22849721) Angew Chem Int Ed Engl. 2014 Sep 26;53(40):10728-32. (PMID: 25111069) J Biol Chem. 2009 Sep 4;284(36):24394-405. (PMID: 19535340) Biochemistry. 2015 May 19;54(19):3037-50. (PMID: 25897714) Sci Rep. 2015 Feb 23;5:8529. (PMID: 25704306) Cell Metab. 2014 Apr 1;19(4):605-17. (PMID: 24703693) J Am Chem Soc. 2012 Feb 1;134(4):1922-5. (PMID: 22263694) Nature. 2013 Apr 4;496(7443):110-3. (PMID: 23552949) |
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 |
تدمد: | 2451-9448 |
---|---|
DOI: | 10.1016/j.chembiol.2017.02.007 |