Molecular modeling of the human eukaryotic translation initiation factor 5A (eIF5A) based on spectroscopic and computational analyses
- Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, 14049-900 Ribeirao Preto (Brazil)
- Department of Chemistry, FFCLRP, University of Sao Paulo, 14040-901 Ribeirao Preto (Brazil)
- Department of Biophysics, Escola Paulista de Medicina, UNIFESP, 04023-062 Sao Paulo (Brazil)
The eukaryotic translation initiation factor 5A (eIF5A) is a protein ubiquitously present in archaea and eukarya, which undergoes a unique two-step post-translational modification called hypusination. Several studies have shown that hypusination is essential for a variety of functional roles for eIF5A, including cell proliferation and synthesis of proteins involved in cell cycle control. Up to now neither a totally selective inhibitor of hypusination nor an inhibitor capable of directly binding to eIF5A has been reported in the literature. The discovery of such an inhibitor might be achieved by computer-aided drug design based on the 3D structure of the human eIF5A. In this study, we present a molecular model for the human eIF5A protein based on the crystal structure of the eIF5A from Leishmania brasiliensis, and compare the modeled conformation of the loop bearing the hypusination site with circular dichroism data obtained with a synthetic peptide of this loop. Furthermore, analysis of amino acid variability between different human eIF5A isoforms revealed peculiar structural characteristics that are of functional relevance.
- OSTI ID:
- 20854436
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 347, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2006.06.119; PII: S0006-291X(06)01426-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
The role of eukaryotic translation initiation factor 5A-1 (eIF5A-1) gene in HPV 16 E6 induces cell growth in human cervical squamous carcinoma cells
The N-terminal region of eukaryotic translation initiation factor 5A signals to nuclear localization of the protein