Object's details: AlkB dioxygenase preferentially repairs protonated substrates: specificity against exocyclic adducts and molecular mechanism of action.

Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
AlkB dioxygenase preferentially repairs protonated substrates: specificity against exocyclic adducts and molecular mechanism of action.
Creator:
Maciejewska, Agnieszka M;
Poznanski, Jaroslaw;
Kaczmarska, Zuzanna;
Krowisz, Beata;
Nieminuszczy, Jadwiga;
Polkowska-Nowakowska, Agnieszka;
Grzesiuk, Elzbieta;
Kusmierek, Jaroslaw T
Description:
Efficient repair by AlkB dioxygenase of exocyclic DNA adducts: 3,N(4)-ethenocytosine, 1,N(6)-ethenoadenine, 3,N(4)- α-hydroxyethanocytosine and, reported here for the first time, 3,N(4)- α-hydroxypropanocytosine, requires higher Fe(II) concentration than the reference 3-methylcytosine. The pH optimum for the repair follows the order of pK(a) values for protonation of the adduct suggesting that positively charged substrates favorably interact with the negatively charged carboxylic group of Asp135 side-chain in the enzyme active centre. This interaction is supported by molecular modeling indicating that 1,N(6)-ethenoadenine and 3,N(4)-ethenocytosine are bound to AlkB more favorably in their protonated cationic forms. An analysis of the pattern of intermolecular interactions that stabilize the location of the ligand points to a role of Asp135 in recognition of the adduct in its protonated form. Moreover, also ab initio calculations underline the role of substrate protonation in lowering the free energy barrier of the transition state of epoxidation of the ethenoadducts studied. The observed time-courses of repair of racemic mixtures of 3,N(4)- α-hydroxyethanocytosine or 3,N(4)- α-hydroxypropanocytosine are unequivocally two-exponential, indicating that the respective stereoisomers are repaired by AlkB with different efficiencies. Molecular modeling of these adducts bound by AlkB allowed evaluation of the participation of their possible conformational states in the enzymatic reaction.
Object availability:
free access
Date:
2012.11.12
Type:
Article;
PeerReviewed
Language:
English
Format:
application/pdf
Relation: http://eprints.ibb.waw.pl/431
Subject:
QD Chemistry;
QR Microbiology
Identifier: http://eprints.ibb.waw.pl/431/1/jbc.M112.353342.full.pdf ;
Maciejewska, Agnieszka M and Poznanski, Jaroslaw and Kaczmarska, Zuzanna and Krowisz, Beata and Nieminuszczy, Jadwiga and Polkowska-Nowakowska, Agnieszka and Grzesiuk, Elzbieta and Kusmierek, Jaroslaw T (2012) AlkB dioxygenase preferentially repairs protonated substrates: specificity against exocyclic adducts and molecular mechanism of action. The Journal of biological chemistry . ISSN 1083-351X (In Press)
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Similar objects

AlkB dioxygenase preferentially repairs protonated substrates: specificity against exocyclic adducts and molecular mechanism of action.

Date:2012.11.12

Type:other

Perturbation of the yeast mitochondrial lipidome and associated membrane proteins following heterologous expression of Artemia-ANT.

Date:2018.04

Type:other

Mapping Protein–Protein Interactions of the Resistance-Related Bacterial Zeta Toxin–Epsilon Antitoxin Complex (ε2ζ2) with High Affinity Peptide Ligands Using Fluorescence Polarization

Date:2016.07.16

Type:other

Lignite biodegradation under conditions of acidic molasses fermentation

Date:2018

Type:other

Live while the DNA lasts. The role of autophagy in DNA loss and survival of diploid yeast cells during chronological aging

Creator:Enkhbaatar, Tuguldur | Skoneczny, Marek | Stępień, Karolina | Mołoń, Mateusz | Skoneczna, Adrianna

Date:2023.10.09

Type:other

New redox-active layer create via epoxy-amine reaction - The base of genosensor for the detection of specific DNA and RNA sequences of avian influenza virus H5N1.

Date:2015.11.04

Type:other

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ ATP Carrier to Bongkrekate in Yeast

Date:2013.09

Type:other

Mitochondrial protein sorting as a therapeutic target for ATP synthase disorders

Date:2014.12.18

Type:other

Federacja Bibliotek Cyfrowych

Object's details: AlkB dioxygenase preferentially repairs protonated substrates: specificity against exocyclic adducts and molecular mechanism of action.

Description

Similar objects