J. Nucl. Phy. Mat. Sci. Rad. A.

In silico Analysis of the Structural Properties of PSMA and its Energetic Relationship with Zn as Cofactor

M.A. Fuentes, L. A. Mandujano, R. López, L.R. Guarneros, E. Azorín, D. Osorio-González

KEYWORDS

PSMA structural analysis, PSMA with and without Zn as cofactor.

PUBLISHED DATE August 6, 2018
PUBLISHER The Author(s) 2018. This article is published with open access at www.chitkara.edu.in/publications.
ABSTRACT

The prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane glycoprotein with enzymatic activity similar to the family of zinc-dependent exopeptidases. This protein is of great medical and pharmacological interest as overexpression in prostate cells is related to the progression of prostate cancer; therefore, it represents an important target for the design of radiopharmaceuticals. The presence of two Zn2+ ions in the active site is crucial to the enzymatic activity and the design of high-affinity inhibitors. The amino acid residues coordinating these ions are highly conserved in PSMA orthologs from plants to mammals, and site-mutagenesis assays of these residues show a loss of enzymatic function or reduction of the kinetic parameters. In the present work, we performed molecular dynamics simulation of PSMA with the purpose of characterizing it energetically and structurally. We elucidated the differences of PSMA with its two Zn+2 ions as cofactors and without them in the free energy profile, and in four structural parameters: root mean square deviations and root mean square fluctuations by atom and amino acid residue, radius of gyration, and solvent accessible surface area.

Page(s) 115-120
URL http://dspace.chitkara.edu.in/jspui/bitstream/123456789/750/1/20_JNP.pdf
ISSN Print : 2321-8649, Online : 2321-9289
DOI 10.15415/jnp.2018.61020
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