Binding leverage as a molecular basis for allosteric regulation.

Allosteric regulation involves conformational transitions or fluctuations between a few closely related states, caused by the binding of effector molecules. We introduce a quantity called binding leverage that measures the ability of a binding site to couple to the intrinsic motions of a protein. We...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Simon Mitternacht, Igor N Berezovsky
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/14584a69fa284588b6eeee6bb0df3baa
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:14584a69fa284588b6eeee6bb0df3baa
record_format	dspace
spelling	oai:doaj.org-article:14584a69fa284588b6eeee6bb0df3baa2021-11-04T05:42:46ZBinding leverage as a molecular basis for allosteric regulation.1553-734X1553-735810.1371/journal.pcbi.1002148https://doaj.org/article/14584a69fa284588b6eeee6bb0df3baa2011-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21935347/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Allosteric regulation involves conformational transitions or fluctuations between a few closely related states, caused by the binding of effector molecules. We introduce a quantity called binding leverage that measures the ability of a binding site to couple to the intrinsic motions of a protein. We use Monte Carlo simulations to generate potential binding sites and either normal modes or pairs of crystal structures to describe relevant motions. We analyze single catalytic domains and multimeric allosteric enzymes with complex regulation. For the majority of the analyzed proteins, we find that both catalytic and allosteric sites have high binding leverage. Furthermore, our analysis of the catabolite activator protein, which is allosteric without conformational change, shows that its regulation involves other types of motion than those modulated at sites with high binding leverage. Our results point to the importance of incorporating dynamic information when predicting functional sites. Because it is possible to calculate binding leverage from a single crystal structure it can be used for characterizing proteins of unknown function and predicting latent allosteric sites in any protein, with implications for drug design.Simon MitternachtIgor N BerezovskyPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 9, p e1002148 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Simon Mitternacht Igor N Berezovsky Binding leverage as a molecular basis for allosteric regulation.
description	Allosteric regulation involves conformational transitions or fluctuations between a few closely related states, caused by the binding of effector molecules. We introduce a quantity called binding leverage that measures the ability of a binding site to couple to the intrinsic motions of a protein. We use Monte Carlo simulations to generate potential binding sites and either normal modes or pairs of crystal structures to describe relevant motions. We analyze single catalytic domains and multimeric allosteric enzymes with complex regulation. For the majority of the analyzed proteins, we find that both catalytic and allosteric sites have high binding leverage. Furthermore, our analysis of the catabolite activator protein, which is allosteric without conformational change, shows that its regulation involves other types of motion than those modulated at sites with high binding leverage. Our results point to the importance of incorporating dynamic information when predicting functional sites. Because it is possible to calculate binding leverage from a single crystal structure it can be used for characterizing proteins of unknown function and predicting latent allosteric sites in any protein, with implications for drug design.
format	article
author	Simon Mitternacht Igor N Berezovsky
author_facet	Simon Mitternacht Igor N Berezovsky
author_sort	Simon Mitternacht
title	Binding leverage as a molecular basis for allosteric regulation.
title_short	Binding leverage as a molecular basis for allosteric regulation.
title_full	Binding leverage as a molecular basis for allosteric regulation.
title_fullStr	Binding leverage as a molecular basis for allosteric regulation.
title_full_unstemmed	Binding leverage as a molecular basis for allosteric regulation.
title_sort	binding leverage as a molecular basis for allosteric regulation.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/14584a69fa284588b6eeee6bb0df3baa
work_keys_str_mv	AT simonmitternacht bindingleverageasamolecularbasisforallostericregulation AT igornberezovsky bindingleverageasamolecularbasisforallostericregulation
_version_	1718445192921481216

Binding leverage as a molecular basis for allosteric regulation.

Ejemplares similares