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, 15 (10), 750-759
eCollection

Insights From Molecular Dynamics Simulation of Human Ceruloplasmin (Ferroxidase Enzyme) Binding With Biogenic Monoamines

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Insights From Molecular Dynamics Simulation of Human Ceruloplasmin (Ferroxidase Enzyme) Binding With Biogenic Monoamines

Bishnu Prasad Mukhopadhyay. Bioinformation.

Abstract

Human ceruloplasmin (hCP) is a multi-copper oxidase with ferroxidase and amine oxidase activities. Molecular dynamics simulation (MDS) and docking analysis of biogenic monoamines with ceruloplasmin explain the role of Asp1025, Glu935, Glu272, Glu232 and Glu230 together with the binding site water molecules (referred as conserved water molecules) in the stabilization of neurotransmitter (Serotonin, Norepinephrine and Epinephrine) molecules within the binding cavity of hCP. Conserved water molecules are found at specific positions interacting with the protein structures that have sequence similarity. The ethylamine side chain nitrogen atom (N1) of neurotransmitter molecules interacts with water molecules in the binding cavity formed by Asp1025, Glu935 and Glu232 residues. These residues form an acidic triad mimicking a substrate binding cavity. The hydroxyl groups attached to the catechol ring of epinephrine and norepinephrine have been stabilized by Asp230 and Asp232 residues. Data suggests that the recognition of biogenic amines mediates through the N+(amine) ...Asp1025-His1026-CuCis-His path. The potential recognition path of biogenic monoamines to trinuclear copper cluster supported by active site water molecules (referred as conserved water molecules) is described in this report.

Keywords: Ceruloplasmin; biogenic monoamines; conserved water molecules.

Conflict of interest statement

Author declares that he has no conflict of interest.

Figures

Figure 1
Figure 1
The RMSD (root mean square deviation) curve for serotonin (red), norepinephrine (blue) and epinephrine (black) during MD-simulation of their complexes with ceruloplasmin
Figure 2
Figure 2
RMSF (root mean square fluctuation) curve of the residues (sequence 900-1040) of ceruloplasmin during MD-simulation of enzyme-biogenic monoamine complexes.
Figure 3
Figure 3
(A).The H-bonding interaction of serotonin with the three conserved water molecules (WS1, WS2 and WS3), Asp1025 and Glu935 is shown. (B) The recognition of serotonin to Cu (T1) center. Direct and water mediated recognition path of serotonin to trinuclear copper center via Cu (T1) center. The nitrogen and oxygen centers have indicated by blue and red colours. The water molecules have shown by red balls
Figure 4
Figure 4
(A).The H-bonding interaction of norepinephrine with the conserved water molecule, Asp1025 and Glu935. (B) The recognition of norepinephrine to Cu (T1) center. Direct and water mediated recognition path of serotonin to trinuclear copper center via Cu (T1) center. The nitrogen and oxygen centers have indicated by blue and red colours. The water molecules have shown by red balls.
Figure 5
Figure 5
(A) The H-bonding interaction of epinephrine with the conserved water molecule, Asp1025 and Glu935. (B) The recognition of epinephrine to Cu (T1) center. Direct and water mediated recognition path of serotonin to trinuclear copper center via Cu (T1) center have shown in the right side of the figure. The nitrogen and oxygen centers have indicated by blue and red colours. The water molecules have shown by red balls.

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