Repository logo
 

Electrostatic Tuning of the Ligand Binding Mechanism by Glu27 in Nitrophorin 7.

Simple item page
cam.issuedOnline2018-07-18
dc.contributor.authorAbbruzzetti, Stefania
dc.contributor.authorAllegri, Alessandro
dc.contributor.authorBidon-Chanal, Axel
dc.contributor.authorOgata, Hideaki
dc.contributor.authorSoavi, Giancarlo
dc.contributor.authorCerullo, Giulio
dc.contributor.authorBruno, Stefano
dc.contributor.authorMontali, Chiara
dc.contributor.authorLuque, F Javier
dc.contributor.authorViappiani, Cristiano
dc.contributor.orcidOgata, Hideaki [0000-0002-2894-2417]
dc.contributor.orcidViappiani, Cristiano [0000-0001-7470-4770]
dc.date.accessioned2018-11-22T00:30:36Z
dc.date.available2018-11-22T00:30:36Z
dc.date.issued2018-07-18
dc.description.abstractNitrophorins (NP) 1-7 are NO-carrying heme proteins found in the saliva of the blood-sucking insect Rhodnius prolixus. The isoform NP7 displays peculiar properties, such as an abnormally high isoelectric point, the ability to bind negatively charged membranes, and a strong pH sensitivity of NO affinity. A unique trait of NP7 is the presence of Glu in position 27, which is occupied by Val in other NPs. Glu27 appears to be important for tuning the heme properties, but its influence on the pH-dependent NO release mechanism, which is assisted by a conformational change in the AB loop, remains unexplored. Here, in order to gain insight into the functional role of Glu27, we examine the effect of Glu27 → Val and Glu27 → Gln mutations on the ligand binding kinetics using CO as a model. The results reveal that annihilation of the negative charge of Glu27 upon mutation reduces the pH sensitivity of the ligand binding rate, a process that in turn depends on the ionization of Asp32. We propose that Glu27 exerts a through-space electrostatic action on Asp32, which shifts the pKa of the latter amino acid towards more acidic values thus reducing the pH sensitivity of the transition between open and closed states.
dc.format.mediumElectronic
dc.identifier.doi10.17863/CAM.32942
dc.identifier.eissn2045-2322
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285588
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/s41598-018-29182-3
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAnimals
dc.subjectCrystallography, X-Ray
dc.subjectGlutamic Acid
dc.subjectHeme
dc.subjectHemeproteins
dc.subjectInsect Proteins
dc.subjectLigands
dc.subjectModels, Molecular
dc.subjectMolecular Dynamics Simulation
dc.subjectMutation
dc.subjectProtein Conformation
dc.subjectRhodnius
dc.subjectSalivary Proteins and Peptides
dc.subjectStatic Electricity
dc.titleElectrostatic Tuning of the Ligand Binding Mechanism by Glu27 in Nitrophorin 7.
dc.typeArticle
dcterms.dateAccepted2018-07-02
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameSci Rep
prism.startingPage10855
prism.volume8
rioxxterms.licenseref.startdate2018-07-18
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41598-018-29182-3

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Electrostatic Tuning of the Ligand Binding Mechanism by Glu27 in Nitrophorin 7.pdf
Size:
2.24 MB
Format:
Adobe Portable Document Format
Description:
Published version
Licence
https://creativecommons.org/licenses/by/4.0/
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
DepositLicenceAgreementv2.1.pdf
Size:
150.9 KB
Format:
Adobe Portable Document Format
Download

Collections

Cambridge University Research Outputs