Crystal structure of a polyglycine hydrolase determined using a RoseTTAFold model.

IF 2.6 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Acta Crystallographica. Section D, Structural Biology Pub Date : 2023-02-01 Epub Date: 2023-02-06 DOI:10.1107/S2059798323000311

Nicole V Dowling, Todd A Naumann, Neil P J Price, David R Rose

{"title":"Crystal structure of a polyglycine hydrolase determined using a RoseTTAFold model.","authors":"Nicole V Dowling, Todd A Naumann, Neil P J Price, David R Rose","doi":"10.1107/S2059798323000311","DOIUrl":null,"url":null,"abstract":"<p><p>Polyglycine hydrolases (PGHs) are secreted fungal proteases that cleave the polyglycine linker of Zea mays ChitA, a defensive chitinase, thus overcoming one mechanism of plant resistance to infection. Despite their importance in agriculture, there has been no previous structural characterization of this family of proteases. The objective of this research was to investigate the proteolytic mechanism and other characteristics by structural and biochemical means. Here, the first atomic structure of a polyglycine hydrolase was identified. It was solved by X-ray crystallography using a RoseTTAFold model, taking advantage of recent technical advances in structure prediction. PGHs are composed of two domains: the N- and C-domains. The N-domain is a novel tertiary fold with an as-yet unknown function that is found across all kingdoms of life. The C-domain shares structural similarities with class C β-lactamases, including a common catalytic nucleophilic serine. In addition to insights into the PGH family and its relationship to β-lactamases, the results demonstrate the power of complementing experimental structure determination with new computational techniques.</p>","PeriodicalId":7116,"journal":{"name":"Acta Crystallographica. Section D, Structural Biology","volume":"79 Pt 2","pages":"168-176"},"PeriodicalIF":2.6000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912923/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Crystallographica. Section D, Structural Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1107/S2059798323000311","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/2/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}

引用次数: 0

Abstract

Polyglycine hydrolases (PGHs) are secreted fungal proteases that cleave the polyglycine linker of Zea mays ChitA, a defensive chitinase, thus overcoming one mechanism of plant resistance to infection. Despite their importance in agriculture, there has been no previous structural characterization of this family of proteases. The objective of this research was to investigate the proteolytic mechanism and other characteristics by structural and biochemical means. Here, the first atomic structure of a polyglycine hydrolase was identified. It was solved by X-ray crystallography using a RoseTTAFold model, taking advantage of recent technical advances in structure prediction. PGHs are composed of two domains: the N- and C-domains. The N-domain is a novel tertiary fold with an as-yet unknown function that is found across all kingdoms of life. The C-domain shares structural similarities with class C β-lactamases, including a common catalytic nucleophilic serine. In addition to insights into the PGH family and its relationship to β-lactamases, the results demonstrate the power of complementing experimental structure determination with new computational techniques.

Abstract Image

查看原文本刊更多论文

使用 RoseTTAFold 模型测定的聚甘氨酸水解酶晶体结构。

聚甘氨酸水解酶（PGHs）是一种分泌型真菌蛋白酶，能裂解玉米甲壳素酶 ChitA 的聚甘氨酸连接体，从而克服植物抗感染的一种机制。尽管这些蛋白酶在农业中非常重要，但以前却没有对这一蛋白酶家族进行结构鉴定。本研究的目的是通过结构和生化手段研究其蛋白水解机制和其他特征。在此，首次确定了聚甘氨酸水解酶的原子结构。利用近年来结构预测技术的进步，通过 X 射线晶体学，使用 RoseTTAFold 模型对其进行了解析。多甘氨酸水解酶由两个结构域组成：N 域和 C 域。N-结构域是一种新颖的三级折叠结构，其功能尚不清楚，在所有生命体中都有发现。C 结构域与 C 类 β-内酰胺酶结构相似，包括一个共同的催化亲核丝氨酸。除了深入了解 PGH 家族及其与 β-内酰胺酶的关系之外，研究结果还证明了利用新的计算技术对实验结构测定进行补充的威力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Acta Crystallographica. Section D, Structural Biology BIOCHEMICAL RESEARCH METHODSBIOCHEMISTRY &-BIOCHEMISTRY & MOLECULAR BIOLOGY

CiteScore

4.50

自引率

13.60%

发文量

216

期刊介绍： Acta Crystallographica Section D welcomes the submission of articles covering any aspect of structural biology, with a particular emphasis on the structures of biological macromolecules or the methods used to determine them. Reports on new structures of biological importance may address the smallest macromolecules to the largest complex molecular machines. These structures may have been determined using any structural biology technique including crystallography, NMR, cryoEM and/or other techniques. The key criterion is that such articles must present significant new insights into biological, chemical or medical sciences. The inclusion of complementary data that support the conclusions drawn from the structural studies (such as binding studies, mass spectrometry, enzyme assays, or analysis of mutants or other modified forms of biological macromolecule) is encouraged. Methods articles may include new approaches to any aspect of biological structure determination or structure analysis but will only be accepted where they focus on new methods that are demonstrated to be of general applicability and importance to structural biology. Articles describing particularly difficult problems in structural biology are also welcomed, if the analysis would provide useful insights to others facing similar problems.