دورية أكاديمية
Human O -GlcNAcase Uses a Preactivated Boat-skew Substrate Conformation for Catalysis. Evidence from X-ray Crystallography and QM/MM Metadynamics.
العنوان: | Human O -GlcNAcase Uses a Preactivated Boat-skew Substrate Conformation for Catalysis. Evidence from X-ray Crystallography and QM/MM Metadynamics. |
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المؤلفون: | Calvelo M; Departament de Química Inorgànica i Orgànica & IQTCUB, Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain., Males A; York Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, York YO10 5DD, United Kingdom., Alteen MG; Department of Chemistry & Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada., Willems LI; York Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, York YO10 5DD, United Kingdom., Vocadlo DJ; Department of Chemistry & Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada., Davies GJ; York Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, York YO10 5DD, United Kingdom., Rovira C; Departament de Química Inorgànica i Orgànica & IQTCUB, Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys, 23, 08020 Barcelona, Spain. |
المصدر: | ACS catalysis [ACS Catal] 2023 Oct 10; Vol. 13 (20), pp. 13672-13678. Date of Electronic Publication: 2023 Oct 10 (Print Publication: 2023). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101562209 Publication Model: eCollection Cited Medium: Print ISSN: 2155-5435 (Print) NLM ISO Abbreviation: ACS Catal Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, c2011- |
مستخلص: | Human O -linked β- N -acetylglucosaminidase (hOGA) is one of the two enzymes involved in nuclear and cytoplasmic protein O-GlcNAcylation, an essential post-translational modification. The enzyme catalyzes the hydrolysis of the GlcNAc- O -(Ser/Thr) glycosidic bonds via anchimeric assistance through the 2-acetamido group of the GlcNAc sugar. However, the conformational itinerary of the GlcNAc ring during catalysis remains unclear. Here we report the crystal structure of wild type hOGA in complex with a nonhydrolyzable glycopeptide substrate and elucidate the full enzyme catalytic mechanism using QM/MM metadynamics. We show that the enzyme can bind the substrate in either a chair- or a boat-like conformation, but only the latter is catalytically competent, leading to the reaction products via 1,4 B / 1 S Competing Interests: The authors declare no competing financial interest. (© 2023 American Chemical Society.) |
References: | Nat Rev Mol Cell Biol. 2020 Dec;21(12):729-749. (PMID: 33087899) Nat Chem Biol. 2017 Jun;13(6):613-615. (PMID: 28346407) Mol Cell. 2014 Jun 5;54(5):820-31. (PMID: 24857547) Science. 2016 Mar 18;351(6279):1293-6. (PMID: 26989246) Carbohydr Res. 2006 Jun 12;341(8):971-82. (PMID: 16584714) J Biol Chem. 2005 Jul 8;280(27):25313-22. (PMID: 15795231) Chem Commun (Camb). 2006 Nov 13;(42):4372-4. (PMID: 17057847) Nat Struct Mol Biol. 2006 Apr;13(4):365-71. (PMID: 16565725) J Phys Chem Lett. 2020 May 7;11(9):3466-3472. (PMID: 32293901) Nature. 2007 Apr 26;446(7139):1017-22. (PMID: 17460662) J Am Chem Soc. 2005 Dec 14;127(49):17202-3. (PMID: 16332065) Eur J Med Chem. 2021 Nov 5;223:113649. (PMID: 34186233) J Chem Theory Comput. 2016 Dec 13;12(12):6157-6168. (PMID: 27951668) Nat Struct Mol Biol. 2015 Nov;22(11):833-4. (PMID: 26581513) J Phys Chem B. 2020 Oct 22;124(42):9310-9322. (PMID: 32970432) Nat Chem Biol. 2017 Jun;13(6):610-612. (PMID: 28346405) Nat Struct Mol Biol. 2019 Nov;26(11):1071-1077. (PMID: 31695185) J Am Chem Soc. 2008 Dec 24;130(51):17620-8. (PMID: 19053474) J Am Chem Soc. 2010 Feb 17;132(6):1807-9. (PMID: 20067256) Brain. 2009 Jul;132(Pt 7):1820-32. (PMID: 19451179) Curr Opin Chem Biol. 2019 Dec;53:131-144. (PMID: 31654859) Chem Rev. 2015 Jun 24;115(12):6217-63. (PMID: 25880693) Nat Chem Biol. 2012 Feb 26;8(4):393-9. (PMID: 22366723) Cell Rep. 2019 Nov 19;29(8):2134-2143.e7. (PMID: 31747588) J Am Chem Soc. 2009 Sep 23;131(37):13415-22. (PMID: 19715310) Nat Commun. 2017 Sep 22;8(1):666. (PMID: 28939839) Curr Opin Chem Biol. 2023 Jun;74:102282. (PMID: 36931022) Nucleic Acids Res. 2022 Jan 7;50(D1):D571-D577. (PMID: 34850161) Angew Chem Int Ed Engl. 2021 Mar 8;60(11):5754-5758. (PMID: 33528085) Biochemistry. 2006 Mar 21;45(11):3835-44. (PMID: 16533067) J Am Chem Soc. 2020 Feb 5;142(5):2120-2124. (PMID: 31917561) Phys Rev Lett. 1996 Oct 28;77(18):3865-3868. (PMID: 10062328) J Biol Chem. 1999 Nov 5;274(45):32015-22. (PMID: 10542233) J Chem Phys. 2020 May 21;152(19):194103. (PMID: 33687235) J Am Chem Soc. 2015 Jun 24;137(24):7528-47. (PMID: 25970019) Nat Struct Mol Biol. 2017 Apr;24(4):362-369. (PMID: 28319083) Acc Chem Res. 2021 Jun 1;54(11):2552-2564. (PMID: 33930267) |
تواريخ الأحداث: | Date Created: 20231116 Latest Revision: 20240212 |
رمز التحديث: | 20240213 |
مُعرف محوري في PubMed: | PMC10636738 |
DOI: | 10.1021/acscatal.3c02378 |
PMID: | 37969138 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2155-5435 |
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DOI: | 10.1021/acscatal.3c02378 |