Abstract
Human Ceruloplasmin (hCP) is an unique multicopper oxidase which involves in different biological functions e.g., iron metabolism, copper transportation, biogenic amine oxidation ,and its malfunction causes Wilson's and Menkes diseases. MD- simulation studies of O2- bound solvated structure have revealed the role of several conserved/ semi-conserved water molecules in the hydration of type-I copper centers and their involvement to recognition dynamics of these metal centers. In O2- bound structure, hydration potentiality of CuRS (Cu1106) type-I copper center is observed to be unique, where two water molecules (W1-W2) are interacting with the metal sites, which was not found in X-ray structures of hCP. Generally, in the interdomain recognition of CuCys-His to CuRS, CuRS to CuPR and CuPR to CuCys-His centers, the copper bound His-residue of one domain interacts with the Glu-residue of other complementary domain through conserved/ semi-conserved (W3 to W5) water- mediated hydrogen bonds (Cu-His...W...Glu), however direct salt-bridge (Cu-His...Glu) interaction were observed in the X- ray structures. The MD- simulated and X- ray structures have indicated some possibilities on the Cu-His...W...Glu ↔ Cu-His...Glu transition during the interdomain recognition of type-I copper centers, which may have some importance in biology and chemistry of ceruloplasmin.
Highlights
IntroductionCeruloplasmin (CP) is an unique multicopper oxidase and it is involved with iron metabolism (ferroxidase activity), copper transportation, catalyzes Cu(I) oxidation, promotes the oxidation of biogenic amines (norepinephrine, epinephrine, and serotonin) and can act as effective anti-oxidant [1]
Ceruloplasmin (CP) is an unique multicopper oxidase and it is involved with iron metabolism, copper transportation, catalyzes Cu(I) oxidation, promotes the oxidation of biogenic amines and can act as effective anti-oxidant [1]
Previous Molecular dynamics (MD)-simulation study of 2J5W PDB structure of CP was indicated the hydration potentiality of trinuclear copper cluster [19], the results could not provide any evidence on the aquation potentiality of Type1 copper centers or on the role of water molecules in the interdomain recognition of Type1 copper center which was thought to be an important aspect concerning to the biology of CP
Summary
Ceruloplasmin (CP) is an unique multicopper oxidase and it is involved with iron metabolism (ferroxidase activity), copper transportation, catalyzes Cu(I) oxidation, promotes the oxidation of biogenic amines (norepinephrine, epinephrine, and serotonin) and can act as effective anti-oxidant [1]. Previous MD-simulation study of 2J5W PDB structure of CP was indicated the hydration potentiality of trinuclear copper cluster [19], the results could not provide any evidence on the aquation potentiality of Type copper centers or on the role of water molecules in the interdomain recognition of Type copper center which was thought to be an important aspect concerning to the biology of CP. To investigate those aspects, MD-simulation study has been followed and carried out the solvated structure of hCP (PDB Id: 4ENZ)
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