The kinetic analysis of recognition of the damaged nucleotides by mutant forms of the 8-oxoguanine DNA glycosylase hOGG1

Standard

The kinetic analysis of recognition of the damaged nucleotides by mutant forms of the 8-oxoguanine DNA glycosylase hOGG1. / Lukina, M. V.; Kuznetsova, A. A.; Kuznetsov, N. A. et al.

In: Russian Journal of Bioorganic Chemistry, Vol. 43, No. 1, 01.01.2017, p. 1-12.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{aab0c030280e480483b014c8e2219a86,

title = "The kinetic analysis of recognition of the damaged nucleotides by mutant forms of the 8-oxoguanine DNA glycosylase hOGG1",

abstract = "We have investigated the role of Tyr-203, His-270, and Lys-249 amino acid residues from the 8-oxoguanine glycosylase (hOGG1) active site in the process of recognition of 7,8-dihydro-8-oxoguanine (oxoG) damaged nucleotide and in the catalytic stages of enzymatic reaction. The pre-steady state kinetic analysis of conformational transitions of mutant forms of the enzyme and model DNA substrates during the enzymatic process revealed that the studied amino acid residues are involved in the specific binding of DNA substrates. The Tyr-203 is responsible for recognition of the damaged nucleotide; interaction between His-270 and DNA is necessary for the formation of the catalytically active complex with the oxoG-containing DNA. The Lys-249 acts not only as one of the catalytically important amino acids of the active site of the enzyme, but also plays a significant role in the formation of specific enzyme–substrate complex. The present study significantly complements the molecular-kinetic model of the enzymatic reaction and helps to clarify the origin of the high specificity of hOGG1 to oxidized bases in DNA.",

keywords = "conformational changes, human 8-oxoguanine DNA glycosylase, mechanism of recognition, pre-steady state kinetics, specificity, SPECIFICITY, STEADY-STATE KINETICS, ACTIVE-SITE, REPAIR ENZYME, CONFORMATIONAL DYNAMICS, SACCHAROMYCES-CEREVISIAE, SUBSTRATE RECOGNITION, FLUORESCENCE, OGG1 PROTEIN, LESION RECOGNITION",

author = "Lukina, {M. V.} and Kuznetsova, {A. A.} and Kuznetsov, {N. A.} and Fedorova, {O. S.}",

year = "2017",

month = jan,

day = "1",

doi = "10.1134/S1068162017010058",

language = "English",

volume = "43",

pages = "1--12",

journal = "Russian Journal of Bioorganic Chemistry",

issn = "1068-1620",

publisher = "MAIK NAUKA/INTERPERIODICA/SPRINGER",

number = "1",

}

RIS

TY - JOUR

T1 - The kinetic analysis of recognition of the damaged nucleotides by mutant forms of the 8-oxoguanine DNA glycosylase hOGG1

AU - Lukina, M. V.

AU - Kuznetsova, A. A.

AU - Kuznetsov, N. A.

AU - Fedorova, O. S.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - We have investigated the role of Tyr-203, His-270, and Lys-249 amino acid residues from the 8-oxoguanine glycosylase (hOGG1) active site in the process of recognition of 7,8-dihydro-8-oxoguanine (oxoG) damaged nucleotide and in the catalytic stages of enzymatic reaction. The pre-steady state kinetic analysis of conformational transitions of mutant forms of the enzyme and model DNA substrates during the enzymatic process revealed that the studied amino acid residues are involved in the specific binding of DNA substrates. The Tyr-203 is responsible for recognition of the damaged nucleotide; interaction between His-270 and DNA is necessary for the formation of the catalytically active complex with the oxoG-containing DNA. The Lys-249 acts not only as one of the catalytically important amino acids of the active site of the enzyme, but also plays a significant role in the formation of specific enzyme–substrate complex. The present study significantly complements the molecular-kinetic model of the enzymatic reaction and helps to clarify the origin of the high specificity of hOGG1 to oxidized bases in DNA.

AB - We have investigated the role of Tyr-203, His-270, and Lys-249 amino acid residues from the 8-oxoguanine glycosylase (hOGG1) active site in the process of recognition of 7,8-dihydro-8-oxoguanine (oxoG) damaged nucleotide and in the catalytic stages of enzymatic reaction. The pre-steady state kinetic analysis of conformational transitions of mutant forms of the enzyme and model DNA substrates during the enzymatic process revealed that the studied amino acid residues are involved in the specific binding of DNA substrates. The Tyr-203 is responsible for recognition of the damaged nucleotide; interaction between His-270 and DNA is necessary for the formation of the catalytically active complex with the oxoG-containing DNA. The Lys-249 acts not only as one of the catalytically important amino acids of the active site of the enzyme, but also plays a significant role in the formation of specific enzyme–substrate complex. The present study significantly complements the molecular-kinetic model of the enzymatic reaction and helps to clarify the origin of the high specificity of hOGG1 to oxidized bases in DNA.

KW - conformational changes

KW - human 8-oxoguanine DNA glycosylase

KW - mechanism of recognition

KW - pre-steady state kinetics

KW - specificity

KW - SPECIFICITY

KW - STEADY-STATE KINETICS

KW - ACTIVE-SITE

KW - REPAIR ENZYME

KW - CONFORMATIONAL DYNAMICS

KW - SACCHAROMYCES-CEREVISIAE

KW - SUBSTRATE RECOGNITION

KW - FLUORESCENCE

KW - OGG1 PROTEIN

KW - LESION RECOGNITION

UR - http://www.scopus.com/inward/record.url?scp=85012927446&partnerID=8YFLogxK

U2 - 10.1134/S1068162017010058

DO - 10.1134/S1068162017010058

M3 - Article

AN - SCOPUS:85012927446

VL - 43

SP - 1

EP - 12

JO - Russian Journal of Bioorganic Chemistry

JF - Russian Journal of Bioorganic Chemistry

SN - 1068-1620

IS - 1

ER -

ID: 8681385