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Title: The Crystal Structure Analysis of Group B Streptococcus Sortase C1: A Model for the ;Lid; Movement upon Substrate Binding

Abstract

A unique feature of the class-C-type sortases, enzymes essential for Gram-positive pilus biogenesis, is the presence of a flexible 'lid' anchored in the active site. However, the mechanistic details of the 'lid' displacement, suggested to be a critical prelude for enzyme catalysis, are not yet known. This is partly due to the absence of enzyme-substrate and enzyme-inhibitor complex crystal structures. We have recently described the crystal structures of the Streptococcus agalactiae SAG2603 V/R sortase SrtC1 in two space groups (type II and type III) and that of its 'lid' mutant and proposed a role of the 'lid' as a protector of the active-site hydrophobic environment. Here, we report the crystal structures of SAG2603 V/R sortase C1 in a different space group (type I) and that of its complex with a small-molecule cysteine protease inhibitor. We observe that the catalytic Cys residue is covalently linked to the small-molecule inhibitor without lid displacement. However, the type I structure provides a view of the sortase SrtC1 lid displacement while having structural elements similar to a substrate sorting motif suitably positioned in the active site. We propose that these major conformational changes seen in the presence of a substrate mimic in the active sitemore » may represent universal features of class C sortase substrate recognition and enzyme activation.« less

Authors:
; ; ; ;  [1]
  1. UAB
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIAID
OSTI Identifier:
1033775
Resource Type:
Journal Article
Journal Name:
Journal of Molecular Biology
Additional Journal Information:
Journal Volume: 414; Journal Issue: 4; Journal ID: ISSN 0022-2836
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; CATALYSIS; CONFORMATIONAL CHANGES; CRYSTAL STRUCTURE; CYSTEINE; ENZYMES; MUTANTS; RESIDUES; SORTING; SPACE GROUPS; STREPTOCOCCUS; SUBSTRATES

Citation Formats

Khare, Baldeep, Fu, Zheng-Qing, Huang, I-Hsiu, Ton-That, Hung, Narayana, Sthanam V.L., Georgia), and UTSMC). The Crystal Structure Analysis of Group B Streptococcus Sortase C1: A Model for the ;Lid; Movement upon Substrate Binding. United States: N. p., 2012. Web. doi:10.1016/j.jmb.2011.10.017.
Khare, Baldeep, Fu, Zheng-Qing, Huang, I-Hsiu, Ton-That, Hung, Narayana, Sthanam V.L., Georgia), & UTSMC). The Crystal Structure Analysis of Group B Streptococcus Sortase C1: A Model for the ;Lid; Movement upon Substrate Binding. United States. doi:10.1016/j.jmb.2011.10.017.
Khare, Baldeep, Fu, Zheng-Qing, Huang, I-Hsiu, Ton-That, Hung, Narayana, Sthanam V.L., Georgia), and UTSMC). Tue . "The Crystal Structure Analysis of Group B Streptococcus Sortase C1: A Model for the ;Lid; Movement upon Substrate Binding". United States. doi:10.1016/j.jmb.2011.10.017.
@article{osti_1033775,
title = {The Crystal Structure Analysis of Group B Streptococcus Sortase C1: A Model for the ;Lid; Movement upon Substrate Binding},
author = {Khare, Baldeep and Fu, Zheng-Qing and Huang, I-Hsiu and Ton-That, Hung and Narayana, Sthanam V.L. and Georgia) and UTSMC)},
abstractNote = {A unique feature of the class-C-type sortases, enzymes essential for Gram-positive pilus biogenesis, is the presence of a flexible 'lid' anchored in the active site. However, the mechanistic details of the 'lid' displacement, suggested to be a critical prelude for enzyme catalysis, are not yet known. This is partly due to the absence of enzyme-substrate and enzyme-inhibitor complex crystal structures. We have recently described the crystal structures of the Streptococcus agalactiae SAG2603 V/R sortase SrtC1 in two space groups (type II and type III) and that of its 'lid' mutant and proposed a role of the 'lid' as a protector of the active-site hydrophobic environment. Here, we report the crystal structures of SAG2603 V/R sortase C1 in a different space group (type I) and that of its complex with a small-molecule cysteine protease inhibitor. We observe that the catalytic Cys residue is covalently linked to the small-molecule inhibitor without lid displacement. However, the type I structure provides a view of the sortase SrtC1 lid displacement while having structural elements similar to a substrate sorting motif suitably positioned in the active site. We propose that these major conformational changes seen in the presence of a substrate mimic in the active site may represent universal features of class C sortase substrate recognition and enzyme activation.},
doi = {10.1016/j.jmb.2011.10.017},
journal = {Journal of Molecular Biology},
issn = {0022-2836},
number = 4,
volume = 414,
place = {United States},
year = {2012},
month = {2}
}