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dc.contributor.author
Swails, Jason M.
dc.contributor.author
Meng, Yilin
dc.contributor.author
Walker, F. Ann
dc.contributor.author
Marti, Marcelo Adrian
dc.contributor.author
Estrin, Dario Ariel
dc.contributor.author
Roitberg, Adrián
dc.date.available
2019-07-27T19:36:42Z
dc.date.issued
2009-01
dc.identifier.citation
Swails, Jason M.; Meng, Yilin; Walker, F. Ann; Marti, Marcelo Adrian; Estrin, Dario Ariel; et al.; pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4; American Chemical Society; Journal of Physical Chemistry B; 113; 4; 1-2009; 1192-1201
dc.identifier.issn
1520-6106
dc.identifier.uri
http://hdl.handle.net/11336/80449
dc.description.abstract
Nitrophorins are NO carrier proteins that transport and release NO through a pH-dependent conformational change. They bind NO tightly in a low pH environment and release it in a higher pH environment. Experimental evidence shows that the increase in the NO dissociation equilibrium constant, K d, is due mainly to an increase in the NO release rate. Structural and kinetic data strongly suggest that NPs control NO escape by modulating its migration from the active site to the solvent through a pH-dependent conformational change. NP2 and NP4 are two representative proteins of the family displaying a 39% overall sequence identity, and interestingly, NP2 releases NO slower than NP4. The proposal that NPs' NO release relies mainly on the NO escape rate makes NPs a very peculiar case among typical heme proteins. The connection between the pH-dependent conformational change and ligand release mechanism is not fully understood and the structural basis for the pH induced structural transition and the different NO release patterns in NPs are unresolved, yet interesting issues. In this work, we have used state of the art molecular dynamics simulations to study the NO escape process in NP2 and NP4 in both the low and high pH states. Our results show that both NPs modulate NO release by switching between a "closed" conformation in a low pH environment and an "open" conformation at higher pH. In both proteins, the change is caused by the differential protonation of a common residue Asp30 in NP4 and Asp29 in NP2, and the NO escape route is conserved. Finally, our results show that, in NP2, the conformational change to the "open" conformation is smaller than that for NP4 which results in a higher barrier for NO release.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Nitrophorin
dc.subject
Molecular Dynamics
dc.subject
Nitric Oxide
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Heme Protein
dc.subject
Chagas Disease
dc.subject.classification
Físico-Química, Ciencia de los Polímeros, Electroquímica
dc.subject.classification
Ciencias Químicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-03-21T16:14:13Z
dc.journal.volume
113
dc.journal.number
4
dc.journal.pagination
1192-1201
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Swails, Jason M.. University of Florida; Estados Unidos
dc.description.fil
Fil: Meng, Yilin. University of Florida; Estados Unidos
dc.description.fil
Fil: Walker, F. Ann. University of Arizona; Estados Unidos
dc.description.fil
Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
dc.description.fil
Fil: Roitberg, Adrián. University of Florida; Estados Unidos
dc.journal.title
Journal of Physical Chemistry B
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/jp806906x
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/jp806906x
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654266/
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