Spectroscopic andTheoreticalStudyofCu Binding to His111 in the HumanPrion ProteinFragment106−115

50. ARCOS-LÓPEZ T, QAYYUM M, RIVILLAS-ACEVEDO L, MIOTTO MC, GRANDE-AZTATZI R, FERNÁNDEZ CO, HEDMAN B, HODGSON KO, VELA A, SOLOMON EI, QUINTANAR L.

INORGANIC CHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2016 vol. 55 p. 2909 - 2922

0020-1669

ABSTRACT:Theabilityofthecellularprionprotein(PrP)CtobindcopperinvivopointstoaphysiologicalroleforPrPincoppertransport.SixcopperbindingsiteshavebeenidentifiedCinthenonstructuredN-terminalregionofhumanPrP.Amongthesesites,theHis111siteisuniqueinthatitcontainsIIIaMKHMmotifthatwouldconferinterestingCuandCuIbindingproperties.WehaveevaluatedCucoordinationtothePrP(106−115)fragmentofthehumanPrPprotein,usingNMRandX-rayabsorptionspectroscopiesandelectronicstructurecalculations.WefindthatMet109andMet112playIan important role in anchoring this metal ion. Cu coordination to His111 is pH-dependent: at pH >8, I2N1O1SspeciesareformedwithoneMetligand;intherangeofpH5−8,bothmethionine(Met)residuesbindtoCu,forminga1N1O2Sspecies,whereNisfromHis111andOisfromabackbonecarbonylorawatermolecule;atpH