pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4
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...
Guardado en:
| Autores principales: | , |
|---|---|
| Publicado: |
2009
|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v113_n4_p1192_Swails http://hdl.handle.net/20.500.12110/paper_15206106_v113_n4_p1192_Swails |
| Aporte de: |
| id |
paper:paper_15206106_v113_n4_p1192_Swails |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_15206106_v113_n4_p1192_Swails2023-06-08T16:19:02Z pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4 Martí, Marcelo Adrián Estrin, Dario Ariel Dynamics Equilibrium constants Molecular dynamics Nitric oxide Porphyrins Active sites Carrier proteins Conformational changes Escape process Escape rates Escape routes Experimental evidences Heme proteins High pH Kinetic datum Molecular dynamics simulations Nitric oxide release No dissociations No release pH dependents Release mechanisms Sequence identities State-of-the arts Structural basis Structural transitions Proteins 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. © 2009 American Chemical Society. Fil:Marti, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v113_n4_p1192_Swails http://hdl.handle.net/20.500.12110/paper_15206106_v113_n4_p1192_Swails |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Dynamics Equilibrium constants Molecular dynamics Nitric oxide Porphyrins Active sites Carrier proteins Conformational changes Escape process Escape rates Escape routes Experimental evidences Heme proteins High pH Kinetic datum Molecular dynamics simulations Nitric oxide release No dissociations No release pH dependents Release mechanisms Sequence identities State-of-the arts Structural basis Structural transitions Proteins |
| spellingShingle |
Dynamics Equilibrium constants Molecular dynamics Nitric oxide Porphyrins Active sites Carrier proteins Conformational changes Escape process Escape rates Escape routes Experimental evidences Heme proteins High pH Kinetic datum Molecular dynamics simulations Nitric oxide release No dissociations No release pH dependents Release mechanisms Sequence identities State-of-the arts Structural basis Structural transitions Proteins Martí, Marcelo Adrián Estrin, Dario Ariel pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4 |
| topic_facet |
Dynamics Equilibrium constants Molecular dynamics Nitric oxide Porphyrins Active sites Carrier proteins Conformational changes Escape process Escape rates Escape routes Experimental evidences Heme proteins High pH Kinetic datum Molecular dynamics simulations Nitric oxide release No dissociations No release pH dependents Release mechanisms Sequence identities State-of-the arts Structural basis Structural transitions Proteins |
| description |
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. © 2009 American Chemical Society. |
| author |
Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_facet |
Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_sort |
Martí, Marcelo Adrián |
| title |
pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4 |
| title_short |
pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4 |
| title_full |
pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4 |
| title_fullStr |
pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4 |
| title_full_unstemmed |
pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4 |
| title_sort |
ph-dependent mechanism of nitric oxide release in nitrophorins 2 and 4 |
| publishDate |
2009 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v113_n4_p1192_Swails http://hdl.handle.net/20.500.12110/paper_15206106_v113_n4_p1192_Swails |
| work_keys_str_mv |
AT martimarceloadrian phdependentmechanismofnitricoxidereleaseinnitrophorins2and4 AT estrindarioariel phdependentmechanismofnitricoxidereleaseinnitrophorins2and4 |
| _version_ |
1768542002469666816 |