Molecular modeling of the human eukaryotic translation initiation factor 5A (eIF5A) based on spectroscopic and computational analyses.
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.
Costa-Neto
Claudio M
CM
Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. claudio@fmrp.usp.br
Parreiras-E-Silva
Lucas T
LT
Ruller
Roberto
R
Oliveira
Eduardo B
EB
Miranda
Antonio
A
Oliveira
Laerte
L
Ward
Richard J
RJ
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D019295:Computational Biology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000737:chemistry* / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D000097574:Eukaryotic Translation Initiation Factor 5A
D010448:Peptide Initiation Factors; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A