Modeling the interplay of glycine protonation and multiple histidine binding of copper in the prion protein octarepeat subdomains
| Autor: | Giovanni La Penna, Francesco Guerrieri, Giancarlo Rossi, Sara Furlan, Velia Minicozzi, Silvia Morante |
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| Rok vydání: | 2008 |
| Předmět: |
Repetitive Sequences
Amino Acid crystal structure Time Factors Prions Glycine Chemical Protonation Biochemistry Repetitive Sequences law.invention Inorganic Chemistry Metal Molecular dynamics chemistry.chemical_compound Deprotonation Models law complex formation Amide Side chain Computer Simulation Histidine Electron paramagnetic resonance density functional theory Binding Sites pH measurement article metal binding X ray crystallography Settore FIS/07 - Fisica Applicata(Beni Culturali Ambientali Biol.e Medicin) Amino Acid Crystallography Models Chemical priority journal chemistry prion protein copper visual_art visual_art.visual_art_medium proton transport Protons glycine histidine Copper |
| Zdroj: | JBIC Journal of Biological Inorganic Chemistry. 14:361-374 |
| ISSN: | 1432-1327 0949-8257 |
| DOI: | 10.1007/s00775-008-0454-8 |
| Popis: | The octarepeat region of the prion protein can bind Cu(2+) ions up to full occupancy (one ion per octarepeat) at neutral pH. While crystallographic data show that the HGGG octarepeat subdomain is the basic binding unit, multiple histidine coordination at lower Cu occupancy has been reported by X-ray absorption spectroscopy, EPR, and potentiometric experiments. In this paper we investigate, with first principles Car-Parrinello simulations, the first step for the formation of the Cu low-level binding mode, where four histidine side chains are coordinated to the same Cu(2+) ion. This step involves the further binding of a second histidine to an already HGGG domain bonded Cu(2+) ion. The influence of the pH on the ability of Cu to bind two histidine side chains was taken into account by simulating different protonation states of the amide N atoms of the two glycines lying nearest to the first histidine. Multiple histidine coordination is also seen to occur when glycine deprotonation occurs and the presence of the extra histidine stabilizes the Cu-peptide complex. Though the stabilization effect slightly decreases with the number of deprotonated glycines (reaching a minimum when both N atoms of the two nearest glycines are available as Cu ligands), the system is still capable of binding the second histidine in a 4N tetrahedral (though slightly distorted) coordination, whose energy is very near to that of the crystallographic square-planar 3N1O coordination. This result suggests that at low metal concentration the reorganization energy associated with Cu(II)/Cu(I) reduction is small also at pH approximately 7, when glycines are deprotonated. |
| Databáze: | OpenAIRE |
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