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Identification of the Catalytic Triad of Family S46 Exopeptidases, Closely Related to Clan PA Endopeptidases

The exopeptidases of family S46 are exceptional, as the closest homologs of these enzymes are the endopeptidases of clan PA. The three-dimensional structure of S46 enzymes is unknown and only one of the catalytic residues, the serine, has been identified. The catalytic histidine and aspartate residu...

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Autores principales: Suzuki, Yoshiyuki, Sakamoto, Yasumitsu, Tanaka, Nobutada, Okada, Hirofumi, Morikawa, Yasushi, Ogasawara, Wataru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944710/
https://www.ncbi.nlm.nih.gov/pubmed/24598890
http://dx.doi.org/10.1038/srep04292
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author Suzuki, Yoshiyuki
Sakamoto, Yasumitsu
Tanaka, Nobutada
Okada, Hirofumi
Morikawa, Yasushi
Ogasawara, Wataru
author_facet Suzuki, Yoshiyuki
Sakamoto, Yasumitsu
Tanaka, Nobutada
Okada, Hirofumi
Morikawa, Yasushi
Ogasawara, Wataru
author_sort Suzuki, Yoshiyuki
collection PubMed
description The exopeptidases of family S46 are exceptional, as the closest homologs of these enzymes are the endopeptidases of clan PA. The three-dimensional structure of S46 enzymes is unknown and only one of the catalytic residues, the serine, has been identified. The catalytic histidine and aspartate residues are not experimentally identified. Here we present phylogenetic and experimental data that identify all residues of the catalytic triad of S46 peptidase, dipeptidyl aminopeptidase BII (DAP BII) from Pseudoxanthomonas mexicana WO24. Phylogenetic comparison with the protein and S46 peptidases, revealed His-86, Ser-657, and five aspartate residues as possible catalytic residues. Mutation studies identified the catalytic triad of DAP BII as His-86, Asp-224, and Ser-657, while secondary structure analysis predicted an extended alpha-helical domain in between Asp-224 and Ser-657. This domain is unique for family S46 exopeptidases and its absence from the endopeptidases of clan PA might be key to their different hydrolysis activities.
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spelling pubmed-39447102014-03-10 Identification of the Catalytic Triad of Family S46 Exopeptidases, Closely Related to Clan PA Endopeptidases Suzuki, Yoshiyuki Sakamoto, Yasumitsu Tanaka, Nobutada Okada, Hirofumi Morikawa, Yasushi Ogasawara, Wataru Sci Rep Article The exopeptidases of family S46 are exceptional, as the closest homologs of these enzymes are the endopeptidases of clan PA. The three-dimensional structure of S46 enzymes is unknown and only one of the catalytic residues, the serine, has been identified. The catalytic histidine and aspartate residues are not experimentally identified. Here we present phylogenetic and experimental data that identify all residues of the catalytic triad of S46 peptidase, dipeptidyl aminopeptidase BII (DAP BII) from Pseudoxanthomonas mexicana WO24. Phylogenetic comparison with the protein and S46 peptidases, revealed His-86, Ser-657, and five aspartate residues as possible catalytic residues. Mutation studies identified the catalytic triad of DAP BII as His-86, Asp-224, and Ser-657, while secondary structure analysis predicted an extended alpha-helical domain in between Asp-224 and Ser-657. This domain is unique for family S46 exopeptidases and its absence from the endopeptidases of clan PA might be key to their different hydrolysis activities. Nature Publishing Group 2014-03-06 /pmc/articles/PMC3944710/ /pubmed/24598890 http://dx.doi.org/10.1038/srep04292 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Suzuki, Yoshiyuki
Sakamoto, Yasumitsu
Tanaka, Nobutada
Okada, Hirofumi
Morikawa, Yasushi
Ogasawara, Wataru
Identification of the Catalytic Triad of Family S46 Exopeptidases, Closely Related to Clan PA Endopeptidases
title Identification of the Catalytic Triad of Family S46 Exopeptidases, Closely Related to Clan PA Endopeptidases
title_full Identification of the Catalytic Triad of Family S46 Exopeptidases, Closely Related to Clan PA Endopeptidases
title_fullStr Identification of the Catalytic Triad of Family S46 Exopeptidases, Closely Related to Clan PA Endopeptidases
title_full_unstemmed Identification of the Catalytic Triad of Family S46 Exopeptidases, Closely Related to Clan PA Endopeptidases
title_short Identification of the Catalytic Triad of Family S46 Exopeptidases, Closely Related to Clan PA Endopeptidases
title_sort identification of the catalytic triad of family s46 exopeptidases, closely related to clan pa endopeptidases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944710/
https://www.ncbi.nlm.nih.gov/pubmed/24598890
http://dx.doi.org/10.1038/srep04292
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