Co-conserved sequence motifs are predictive of substrate specificity in a family of monotopic phosphoglycosyl transferases.
Co-conserved sequence motifs are predictive of substrate specificity in a family of monotopic phosphoglycosyl transferases.
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DOI：
10.1002/pro.4646
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发表时间：
2023-06
期刊：
影响因子：
8
通讯作者：
Imperiali, Barbara
中科院分区：
文献类型：
--
作者：
Anderson, Alyssa J. J.;Dodge, Greg J. J.;Allen, Karen N. N.;Imperiali, Barbara
关键词：
单聚磷酸糖基转移酶（Monotopic phosphoglycosyl transferases，monoPGTs）是一个广泛的酶超家族，催化细菌糖缀合物生物合成中的第一个膜定位步骤。MonoPGTs对其同源核苷酸二磷酸糖（NDP-糖）底物显示出强烈的偏好。然而，尽管通过先前开发的包含> 38，000个非冗余序列的序列相似性网络对monoPGT超家族进行了广泛表征，但monoPGT序列与NDP-糖底物特异性之间的联系仍然难以捉摸。在这项工作中，我们首次从结构上表征了原型monoPGT的C末端，并表明19个C末端残基在monoPGT的一个子集中起着重要的结构作用。这种新的结构信息有助于鉴定预测该monoPGTs子集的NDP-糖底物特异性的共保守序列“指纹”。产生了隐马尔可夫模型，其正确地分配了先前未注释的monoPGTs的底物。总之，这些结构、序列和生化分析为指导monoPGTs底物特异性的决定因素提供了新的见解，并提供了一种策略，用于分配使用UDP-二-N-乙酰基杆菌胺的超家族中酶亚组的NDP-糖底物。展望未来，这种方法可以应用于鉴定作为不同UDP-糖底物特异性的monoPGTs指纹的其他序列基序。
Monotopic phosphoglycosyl transferases (monoPGTs) are an expansive superfamily of enzymes that catalyze the first membrane‐committed step in the biosynthesis of bacterial glycoconjugates. MonoPGTs show a strong preference for their cognate nucleotide diphospho‐sugar (NDP‐sugar) substrates. However, despite extensive characterization of the monoPGT superfamily through previous development of a sequence similarity network comprising >38,000 nonredundant sequences, the connection between monoPGT sequence and NDP‐sugar substrate specificity has remained elusive. In this work, we structurally characterize the C‐terminus of a prototypic monoPGT for the first time and show that 19 C‐terminal residues play a significant structural role in a subset of monoPGTs. This new structural information facilitated the identification of co‐conserved sequence “fingerprints” that predict NDP‐sugar substrate specificity for this subset of monoPGTs. A Hidden Markov model was generated that correctly assigned the substrate of previously unannotated monoPGTs. Together, these structural, sequence, and biochemical analyses have delivered new insight into the determinants guiding substrate specificity of monoPGTs and have provided a strategy for assigning the NDP‐sugar substrate of a subset of enzymes in the superfamily that use UDP‐di‐N‐acetyl bacillosamine. Moving forward, this approach may be applied to identify additional sequence motifs that serve as fingerprints for monoPGTs of differing UDP‐sugar substrate specificity.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
8
作者：
Frank, BS;Vardar, D;McKnight, CJ
通讯作者：
McKnight, CJ
影响因子：
3.2
作者：
Cartee, RT;Forsee, WT;Yother, J
通讯作者：
Yother, J
影响因子：
3.6
作者：
Linton, D;Dorrell, N;Wren, BW
通讯作者：
Wren, BW
DOI：
10.1107/s0907444908040006
发表时间：
2009-02-01
影响因子：
2.2
作者：
Karmali, Anjum M.;Blundell, Tom L.;Furnham, Nicholas
通讯作者：
Furnham, Nicholas