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Putative role of conserved water molecules in the hydration and inter-domain recognition of mono nuclear copper centers in O2-bound human ceruloplasmin: A comparative study between X-ray and MD simulated structures



Bishnu Prasad Mukhopadhyay



Department of Chemistry National Institute of Technology-Durgapur, West Bengal, Durgapur - 713209, India



Bishnu P. Mukhopadhyay - E-mail address:;; Phone: +91- 0343 Ė 2547074; Fax: +91-0343-2547375 / 2546753; *Corresponding author


Article Type

Research Article



Received May 8, 2019; Accepted June 2, 2019; Published June 15, 2019



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 Wilsonís 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.



Ceruloplasmin; multicopper oxidase; Type-1 copper centers; MD- simulation; conserved water molecules



Mukhopadhyay, Bioinformation 15(6): 402-411 (2019)


Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.