Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity

TEM-1 β-lactamase evolved from ancestral enzymes that degraded a variety of β-lactam antibiotics with moderate efficiency and degrades β-lactam antibiotics with a strong preference for penicillins. Here authors developed a computational approach to rationally mold a protein flexibility profile on th...

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Autores principales: Tushar Modi, Valeria A. Risso, Sergio Martinez-Rodriguez, Jose A. Gavira, Mubark D. Mebrat, Wade D. Van Horn, Jose M. Sanchez-Ruiz, S. Banu Ozkan
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/9f68b130500b474887f6a03663bb2f12
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spelling oai:doaj.org-article:9f68b130500b474887f6a03663bb2f122021-12-02T11:44:56ZHinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity10.1038/s41467-021-22089-02041-1723https://doaj.org/article/9f68b130500b474887f6a03663bb2f122021-03-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-22089-0https://doaj.org/toc/2041-1723TEM-1 β-lactamase evolved from ancestral enzymes that degraded a variety of β-lactam antibiotics with moderate efficiency and degrades β-lactam antibiotics with a strong preference for penicillins. Here authors developed a computational approach to rationally mold a protein flexibility profile on the basis of a hinge-shift mechanism and show a putative Precambrian β-lactamase that mimics the modern TEM-1 β-lactamase with only 21 amino acid replacements.Tushar ModiValeria A. RissoSergio Martinez-RodriguezJose A. GaviraMubark D. MebratWade D. Van HornJose M. Sanchez-RuizS. Banu OzkanNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Science
Q
spellingShingle Science
Q
Tushar Modi
Valeria A. Risso
Sergio Martinez-Rodriguez
Jose A. Gavira
Mubark D. Mebrat
Wade D. Van Horn
Jose M. Sanchez-Ruiz
S. Banu Ozkan
Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity
description TEM-1 β-lactamase evolved from ancestral enzymes that degraded a variety of β-lactam antibiotics with moderate efficiency and degrades β-lactam antibiotics with a strong preference for penicillins. Here authors developed a computational approach to rationally mold a protein flexibility profile on the basis of a hinge-shift mechanism and show a putative Precambrian β-lactamase that mimics the modern TEM-1 β-lactamase with only 21 amino acid replacements.
format article
author Tushar Modi
Valeria A. Risso
Sergio Martinez-Rodriguez
Jose A. Gavira
Mubark D. Mebrat
Wade D. Van Horn
Jose M. Sanchez-Ruiz
S. Banu Ozkan
author_facet Tushar Modi
Valeria A. Risso
Sergio Martinez-Rodriguez
Jose A. Gavira
Mubark D. Mebrat
Wade D. Van Horn
Jose M. Sanchez-Ruiz
S. Banu Ozkan
author_sort Tushar Modi
title Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity
title_short Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity
title_full Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity
title_fullStr Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity
title_full_unstemmed Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity
title_sort hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/9f68b130500b474887f6a03663bb2f12
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