Characterization of a novel domain 'GATE' in the ABC protein DrrA and its role in drug efflux by the DrrAB complex.
Characterization of a novel domain 'GATE' in the ABC protein DrrA and its role in drug efflux by the DrrAB complex.
复制标题
ABC 蛋白 DrrA 中新结构域“GATE”的表征及其在 DrrAB 复合物药物流出中的作用。
DOI：
10.1016/j.bbrc.2015.02.086
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发表时间：
2015
影响因子：
3.1
通讯作者：
Kaur,Parjit
中科院分区：
文献类型：
--
作者：
Zhang,Han;Rahman,Sadia;Li,Wen;Fu,Guoxing;Kaur,Parjit
A novel domain, GATE (Glycine-loopAndTransducerElement), 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.
