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Structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the D domain of ADAMalysin family proteins

The structures of snake venom metalloproteases (SVMPs) are proposed to be useful models to understand the structural and functional relationship of ADAM (a disintegrin and metalloprotease) which are membrane-anchored proteins involved in multiple human diseases. We have purified, sequenced and deter...

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Autores principales: Guan, Hong-Hsiang, Goh, King-Siang, Davamani, Fabian, Wu, Po-Long, Huang, Yen-Wei, Jeyakanthan, Jeyaraman, Wu, Wen-guey, Chen, Chun-Jung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier Inc. 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129284/
https://www.ncbi.nlm.nih.gov/pubmed/19932752
http://dx.doi.org/10.1016/j.jsb.2009.11.009
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author Guan, Hong-Hsiang
Goh, King-Siang
Davamani, Fabian
Wu, Po-Long
Huang, Yen-Wei
Jeyakanthan, Jeyaraman
Wu, Wen-guey
Chen, Chun-Jung
author_facet Guan, Hong-Hsiang
Goh, King-Siang
Davamani, Fabian
Wu, Po-Long
Huang, Yen-Wei
Jeyakanthan, Jeyaraman
Wu, Wen-guey
Chen, Chun-Jung
author_sort Guan, Hong-Hsiang
collection PubMed
description The structures of snake venom metalloproteases (SVMPs) are proposed to be useful models to understand the structural and functional relationship of ADAM (a disintegrin and metalloprotease) which are membrane-anchored proteins involved in multiple human diseases. We have purified, sequenced and determined the structures of two new P-III SVMPs – atragin and kaouthiagin-like (K-like) from Naja atra. Atragin exhibits a known C-shaped topology, whereas K-like adopts an I-shaped conformation because of the distinct disulfide pattern in the disintegrin-like (D) domain. K-like exhibits an enzymatic specificity toward pro-TNFα with less inhibition of cell migration, but atragin shows the opposite effect. The specificity of the enzymatic activity is indicated to be dominated mainly by the local structures of SVMP in the metalloprotease (M) domain, whereas the hyper-variable region (HVR) in the cysteine-rich (C) domain is involved in a cell-migration activity. We demonstrate also a pH-dependent enzymatic activity of atragin that we correlate with the structural dynamics of a Zn(2+)-binding motif and the Met-turn based on the structures determined with a pH-jump method. The structural variations between the C- and I-shapes highlight the disulfide bond patterns in the D domain of the ADAM/adamalysin/reprolysins family proteins.
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spelling pubmed-71292842020-04-08 Structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the D domain of ADAMalysin family proteins Guan, Hong-Hsiang Goh, King-Siang Davamani, Fabian Wu, Po-Long Huang, Yen-Wei Jeyakanthan, Jeyaraman Wu, Wen-guey Chen, Chun-Jung J Struct Biol Article The structures of snake venom metalloproteases (SVMPs) are proposed to be useful models to understand the structural and functional relationship of ADAM (a disintegrin and metalloprotease) which are membrane-anchored proteins involved in multiple human diseases. We have purified, sequenced and determined the structures of two new P-III SVMPs – atragin and kaouthiagin-like (K-like) from Naja atra. Atragin exhibits a known C-shaped topology, whereas K-like adopts an I-shaped conformation because of the distinct disulfide pattern in the disintegrin-like (D) domain. K-like exhibits an enzymatic specificity toward pro-TNFα with less inhibition of cell migration, but atragin shows the opposite effect. The specificity of the enzymatic activity is indicated to be dominated mainly by the local structures of SVMP in the metalloprotease (M) domain, whereas the hyper-variable region (HVR) in the cysteine-rich (C) domain is involved in a cell-migration activity. We demonstrate also a pH-dependent enzymatic activity of atragin that we correlate with the structural dynamics of a Zn(2+)-binding motif and the Met-turn based on the structures determined with a pH-jump method. The structural variations between the C- and I-shapes highlight the disulfide bond patterns in the D domain of the ADAM/adamalysin/reprolysins family proteins. Published by Elsevier Inc. 2010-03 2009-11-22 /pmc/articles/PMC7129284/ /pubmed/19932752 http://dx.doi.org/10.1016/j.jsb.2009.11.009 Text en Crown copyright © 2009 Published by Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Guan, Hong-Hsiang
Goh, King-Siang
Davamani, Fabian
Wu, Po-Long
Huang, Yen-Wei
Jeyakanthan, Jeyaraman
Wu, Wen-guey
Chen, Chun-Jung
Structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the D domain of ADAMalysin family proteins
title Structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the D domain of ADAMalysin family proteins
title_full Structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the D domain of ADAMalysin family proteins
title_fullStr Structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the D domain of ADAMalysin family proteins
title_full_unstemmed Structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the D domain of ADAMalysin family proteins
title_short Structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the D domain of ADAMalysin family proteins
title_sort structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the d domain of adamalysin family proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129284/
https://www.ncbi.nlm.nih.gov/pubmed/19932752
http://dx.doi.org/10.1016/j.jsb.2009.11.009
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