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Title: Characterization of a novel domain ‘GATE’ in the ABC protein DrrA and its role in drug efflux by the DrrAB complex

Abstract

A novel domain, GATE (Glycine-loop And Transducer Element), is identified in the ABC protein DrrA. This domain shows sequence and structural conservation among close homologs of DrrA as well as distantly-related ABC proteins. Among the highly conserved residues in this domain are three glycines, G215, G221 and G231, of which G215 was found to be critical for stable expression of the DrrAB complex. Other conserved residues, including E201, G221, K227 and G231, were found to be critical for the catalytic and transport functions of the DrrAB transporter. Structural analysis of both the previously published crystal structure of the DrrA homolog MalK and the modeled structure of DrrA showed that G215 makes close contacts with residues in and around the Walker A motif, suggesting that these interactions may be critical for maintaining the integrity of the ATP binding pocket as well as the complex. It is also shown that G215A or K227R mutation diminishes some of the atomic interactions essential for ATP catalysis and overall transport function. Therefore, based on both the biochemical and structural analyses, it is proposed that the GATE domain, located outside of the previously identified ATP binding and hydrolysis motifs, is an additional element involved in ATPmore » catalysis. - Highlights: • A novel domain ‘GATE’ is identified in the ABC protein DrrA. • GATE shows high sequence and structural conservation among diverse ABC proteins. • GATE is located outside of the previously studied ATP binding and hydrolysis motifs. • Conserved GATE residues are critical for stability of DrrAB and for ATP catalysis.« less

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
22461984
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 459; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ATP; CATALYSIS; CRYSTAL STRUCTURE; DOXORUBICIN; GLYCINE; HYDROLYSIS; MUTATIONS; PROTEINS; RESIDUES; STABILITY; TRANSDUCERS

Citation Formats

Zhang, Han, Rahman, Sadia, Li, Wen, Fu, Guoxing, and Kaur, Parjit, E-mail: pkaur@gsu.edu. Characterization of a novel domain ‘GATE’ in the ABC protein DrrA and its role in drug efflux by the DrrAB complex. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.02.086.
Zhang, Han, Rahman, Sadia, Li, Wen, Fu, Guoxing, & Kaur, Parjit, E-mail: pkaur@gsu.edu. Characterization of a novel domain ‘GATE’ in the ABC protein DrrA and its role in drug efflux by the DrrAB complex. United States. doi:10.1016/J.BBRC.2015.02.086.
Zhang, Han, Rahman, Sadia, Li, Wen, Fu, Guoxing, and Kaur, Parjit, E-mail: pkaur@gsu.edu. Fri . "Characterization of a novel domain ‘GATE’ in the ABC protein DrrA and its role in drug efflux by the DrrAB complex". United States. doi:10.1016/J.BBRC.2015.02.086.
@article{osti_22461984,
title = {Characterization of a novel domain ‘GATE’ in the ABC protein DrrA and its role in drug efflux by the DrrAB complex},
author = {Zhang, Han and Rahman, Sadia and Li, Wen and Fu, Guoxing and Kaur, Parjit, E-mail: pkaur@gsu.edu},
abstractNote = {A novel domain, GATE (Glycine-loop And Transducer Element), is identified in the ABC protein DrrA. This domain shows sequence and structural conservation among close homologs of DrrA as well as distantly-related ABC proteins. Among the highly conserved residues in this domain are three glycines, G215, G221 and G231, of which G215 was found to be critical for stable expression of the DrrAB complex. Other conserved residues, including E201, G221, K227 and G231, were found to be critical for the catalytic and transport functions of the DrrAB transporter. Structural analysis of both the previously published crystal structure of the DrrA homolog MalK and the modeled structure of DrrA showed that G215 makes close contacts with residues in and around the Walker A motif, suggesting that these interactions may be critical for maintaining the integrity of the ATP binding pocket as well as the complex. It is also shown that G215A or K227R mutation diminishes some of the atomic interactions essential for ATP catalysis and overall transport function. Therefore, based on both the biochemical and structural analyses, it is proposed that the GATE domain, located outside of the previously identified ATP binding and hydrolysis motifs, is an additional element involved in ATP catalysis. - Highlights: • A novel domain ‘GATE’ is identified in the ABC protein DrrA. • GATE shows high sequence and structural conservation among diverse ABC proteins. • GATE is located outside of the previously studied ATP binding and hydrolysis motifs. • Conserved GATE residues are critical for stability of DrrAB and for ATP catalysis.},
doi = {10.1016/J.BBRC.2015.02.086},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 459,
place = {United States},
year = {Fri Mar 27 00:00:00 EDT 2015},
month = {Fri Mar 27 00:00:00 EDT 2015}
}