Structural genomics analysis of uncharacterized protein families overrepresented in human gut bacteria identifies a novel glycoside hydrolase.

Structural genomics analysis of uncharacterized protein families overrepresented in human gut bacteria identifies a novel glycoside hydrolase.
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DOI:
10.1186/1471-2105-15-112
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发表时间:
2014-04-17
期刊:
影响因子:
3
通讯作者:
Godzik A
Godzik A
中科院分区:
生物学4区
文献类型:
--
作者:
Sheydina A;Eberhardt RY;Rigden DJ;Chang Y;Li Z;Zmasek CC;Axelrod HL;Godzik A

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拟杆菌是我们肠道微生物群的重要组成部分,以优化多种多糖的代谢而闻名。对拟杆菌(Bacteroides thetaiotaomicron)基因组的初步分析鉴定出172个糖基水解酶和大量与多糖代谢相关的未表征蛋白。BT_1012来自拟杆菌(Bacteroides thetaiotaomicron VPI-5482),是一种功能未知的蛋白质,是一个完全由未知蛋白质组成的大蛋白质家族的成员。初始序列分析预测该蛋白具有两个结构域,一个在N端,一个在c端。一个PSI-BLAST搜索发现超过150个全长和超过90个半大小同源物仅由n端结构域组成。实验确定的BT_1012蛋白的三维结构证实了它的双结构域结构,两个结构域的结构分析表明了它们的特定功能。n端结构域是一个假定的催化结构域,与已知的糖苷水解酶具有显著的相似性,c端结构域具有β -三明治折叠,通常在其他糖基水解酶的c端结构域中发现,然而这些结构域通常参与底物结合。我们描述了BT_1012蛋白的结构,并讨论了其序列-结构关系及其可能的功能意义。BT_1012蛋白的结构和序列分析确定它是一种糖基水解酶,扩大了在拟杆菌属中参与多糖代谢的酶的目录。基于此,我们将BT_1012蛋白中发现的两个结构域PF13204和PF12904的Pfam家族分别命名为假定的糖苷水解酶和糖苷水解酶相关的c端结构域。
Bacteroides spp. form a significant part of our gut microbiome and are well known for optimized metabolism of diverse polysaccharides. Initial analysis of the archetypal Bacteroides thetaiotaomicron genome identified 172 glycosyl hydrolases and a large number of uncharacterized proteins associated with polysaccharide metabolism. BT_1012 from Bacteroides thetaiotaomicron VPI-5482 is a protein of unknown function and a member of a large protein family consisting entirely of uncharacterized proteins. Initial sequence analysis predicted that this protein has two domains, one on the N- and one on the C-terminal. A PSI-BLAST search found over 150 full length and over 90 half size homologs consisting only of the N-terminal domain. The experimentally determined three-dimensional structure of the BT_1012 protein confirms its two-domain architecture and structural analysis of both domains suggests their specific functions. The N-terminal domain is a putative catalytic domain with significant similarity to known glycoside hydrolases, the C-terminal domain has a beta-sandwich fold typically found in C-terminal domains of other glycosyl hydrolases, however these domains are typically involved in substrate binding. We describe the structure of the BT_1012 protein and discuss its sequence-structure relationship and their possible functional implications. Structural and sequence analyses of the BT_1012 protein identifies it as a glycosyl hydrolase, expanding an already impressive catalog of enzymes involved in polysaccharide metabolism in Bacteroides spp. Based on this we have renamed the Pfam families representing the two domains found in the BT_1012 protein, PF13204 and PF12904, as putative glycoside hydrolase and glycoside hydrolase-associated C-terminal domain respectively.
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