The Mechanism of the Glycosylase Reaction with HOGG1 Base-excision Repair Enzyme: Concerted Effect of Lys249 and Asp268 During Excision of 8-oxoguanine

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2017 Mar 24

PMID 28334993

Citations 3

Authors

Jakub Sebera

Yoshikazu Hattori

Daichi Sato

David reha

Radim Nencka

Takashi Kohno

Chojiro Kojima

Yoshiyuki Tanaka

Vladimir Sychrovsky

Affiliations

Soon will be listed here.

Abstract

The excision of 8-oxoguanine (oxoG) by the human 8-oxoguanine DNA glycosylase 1 (hOGG1) base-excision repair enzyme was studied by using the QM/MM (M06-2X/6-31G(d,p):OPLS2005) calculation method and nuclear magnetic resonance (NMR) spectroscopy. The calculated glycosylase reaction included excision of the oxoG base, formation of Lys249-ribose enzyme-substrate covalent adduct and formation of a Schiff base. The formation of a Schiff base with ΔG# = 17.7 kcal/mol was the rate-limiting step of the reaction. The excision of the oxoG base with ΔG# = 16.1 kcal/mol proceeded via substitution of the C1΄-N9 N-glycosidic bond with an H-N9 bond where the negative charge on the oxoG base and the positive charge on the ribose were compensated in a concerted manner by NH3+(Lys249) and CO2-(Asp268), respectively. The effect of Asp268 on the oxoG excision was demonstrated with 1H NMR for WT hOGG1 and the hOGG1(D268N) mutant: the excision of oxoG was notably suppressed when Asp268 was mutated to Asn. The loss of the base-excision function was rationalized with QM/MM calculations and Asp268 was confirmed as the electrostatic stabilizer of ribose oxocarbenium through the initial base-excision step of DNA repair. The NMR experiments and QM/MM calculations consistently illustrated the base-excision reaction operated by hOGG1.

Citing Articles

Assessment of hOGG1 Genetic Polymorphism (rs1052133) and DNA Damage in Radiation-Exposed Workers.

Surniyantoro H, Yusuf D, Rahardjo T, Rahajeng N, Kisnanto T, Nurhayati S Asian Pac J Cancer Prev. 2022; 23(12):4005-4012.

PMID: 36579980 PMC: 9971479. DOI: 10.31557/APJCP.2022.23.12.4005.

Hexavalent chromium disrupts chromatin architecture.

VonHandorf A, Zablon H, Puga A Semin Cancer Biol. 2021; 76:54-60.

PMID: 34274487 PMC: 8627925. DOI: 10.1016/j.semcancer.2021.07.009.

Association Between the hOGG1 1245C>G (rs1052133) Polymorphism and Susceptibility to Colorectal Cancer: a Meta-analysis Based on 7010 Cases and 10,674 Controls.

Ghelmani Y, Asadian F, Antikchi M, Dastgheib S, Shaker S, Jafari-Nedooshan J J Gastrointest Cancer. 2020; 52(2):389-398.

PMID: 33025423 DOI: 10.1007/s12029-020-00532-7.

References

David S, OShea V, Kundu S . Base-excision repair of oxidative DNA damage. Nature. 2007; 447(7147):941-50. PMC: 2896554. DOI: 10.1038/nature05978. View

Sychrovsky V, Vokacova Z, Trantirek L . Guanine bases in DNA G-quadruplex adopt nonplanar geometries owing to solvation and base pairing. J Phys Chem A. 2012; 116(16):4144-51. DOI: 10.1021/jp2110049. View

Boiteux S, Radicella J . The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. Arch Biochem Biophys. 2000; 377(1):1-8. DOI: 10.1006/abbi.2000.1773. View

Lee S, Radom C, Verdine G . Trapping and structural elucidation of a very advanced intermediate in the lesion-extrusion pathway of hOGG1. J Am Chem Soc. 2008; 130(25):7784-5. PMC: 2878488. DOI: 10.1021/ja800821t. View

Radicella J, Dherin C, Desmaze C, Fox M, Boiteux S . Cloning and characterization of hOGG1, a human homolog of the OGG1 gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1997; 94(15):8010-5. PMC: 21547. DOI: 10.1073/pnas.94.15.8010. View

Bruner S, Norman D, Verdine G . Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature. 2000; 403(6772):859-66. DOI: 10.1038/35002510. View

Berti P, McCann J . Toward a detailed understanding of base excision repair enzymes: transition state and mechanistic analyses of N-glycoside hydrolysis and N-glycoside transfer. Chem Rev. 2006; 106(2):506-55. DOI: 10.1021/cr040461t. View

Tanaka Y, Oda S, Yamaguchi H, Kondo Y, Kojima C, Ono A . 15N-15N J-coupling across Hg(II): direct observation of Hg(II)-mediated T-T base pairs in a DNA duplex. J Am Chem Soc. 2007; 129(2):244-5. DOI: 10.1021/ja065552h. View

Yin Y, Sasaki S, Taniguchi Y . Recognition and excision properties of 8-halogenated-7-deaza-2'-deoxyguanosine as 8-oxo-2'-deoxyguanosine analogues and Fpg and hOGG1 inhibitors. Chembiochem. 2015; 16(8):1190-8. DOI: 10.1002/cbic.201402690. View

10.

Warshel A, Sharma P, Kato M, Xiang Y, Liu H, Olsson M . Electrostatic basis for enzyme catalysis. Chem Rev. 2006; 106(8):3210-35. DOI: 10.1021/cr0503106. View

11.

Roldan-Arjona T, Wei Y, Carter K, Klungland A, Anselmino C, Wang R . Molecular cloning and functional expression of a human cDNA encoding the antimutator enzyme 8-hydroxyguanine-DNA glycosylase. Proc Natl Acad Sci U S A. 1997; 94(15):8016-20. PMC: 21548. DOI: 10.1073/pnas.94.15.8016. View

12.

Arai K, Morishita K, Shinmura K, Kohno T, Kim S, Nohmi T . Cloning of a human homolog of the yeast OGG1 gene that is involved in the repair of oxidative DNA damage. Oncogene. 1997; 14(23):2857-61. DOI: 10.1038/sj.onc.1201139. View

13.

Donley N, Jaruga P, Coskun E, Dizdaroglu M, McCullough A, Lloyd R . Small Molecule Inhibitors of 8-Oxoguanine DNA Glycosylase-1 (OGG1). ACS Chem Biol. 2015; 10(10):2334-43. PMC: 4894821. DOI: 10.1021/acschembio.5b00452. View

14.

Nash H, Lu R, Lane W, Verdine G . The critical active-site amine of the human 8-oxoguanine DNA glycosylase, hOgg1: direct identification, ablation and chemical reconstitution. Chem Biol. 1997; 4(9):693-702. DOI: 10.1016/s1074-5521(97)90225-8. View

15.

Hamm M, Gill T, Nicolson S, Summers M . Substrate specificity of Fpg (MutM) and hOGG1, two repair glycosylases. J Am Chem Soc. 2007; 129(25):7724-5. DOI: 10.1021/ja0716453. View

16.

Helleday T, Petermann E, Lundin C, Hodgson B, Sharma R . DNA repair pathways as targets for cancer therapy. Nat Rev Cancer. 2008; 8(3):193-204. DOI: 10.1038/nrc2342. View

17.

Kellie J, Wilson K, Wetmore S . An ONIOM and MD Investigation of Possible Monofunctional Activity of Human 8-Oxoguanine-DNA Glycosylase (hOgg1). J Phys Chem B. 2015; 119(25):8013-23. DOI: 10.1021/acs.jpcb.5b04051. View

18.

Radom C, Banerjee A, Verdine G . Structural characterization of human 8-oxoguanine DNA glycosylase variants bearing active site mutations. J Biol Chem. 2006; 282(12):9182-94. DOI: 10.1074/jbc.M608989200. View

19.

Lindahl T, Wood R . Quality control by DNA repair. Science. 1999; 286(5446):1897-905. DOI: 10.1126/science.286.5446.1897. View

20.

Fromme J, Verdine G . Structure of a trapped endonuclease III-DNA covalent intermediate. EMBO J. 2003; 22(13):3461-71. PMC: 165637. DOI: 10.1093/emboj/cdg311. View