In silico analysis of the adenylation domains of the freestanding enzymes belonging to the eucaryotic nonribosomal peptide synthetase-like family.
This work presents a computational analysis of the molecular characteristics shared by the adenylation domains from traditional nonribosomal peptide synthetases (NRPSs) and the group of the freestanding homologous enzymes: alpha-aminoadipate semialdehyde dehydrogenase, alpha-aminoadipate reductase and the protein Ebony. The results of systematic sequence comparisons allow us to conclude that a specificity-conferring code, similar to that described for the NRPSs, can be recognized in such enzymes. The structural and functional roles of the residues involved in the substrate selection and binding are proposed through the analysis of the predicted interactions of the model active sites and their respective substrates. The indications deriving from this study can be useful for the programming of experiments aimed at a better characterization and at the engineering of this emerging group of single NRPS modules that are responsible for amino acid selection, activation and modification in the absence of other NRPS assembly line components.
Di Vincenzo
Leonardo
L
Dipartimento di Scienze Biochimiche A. Rossi Fanelli, Università di Roma La Sapienza, Roma, Italy.
Grgurina
Ingeborg
I
Pascarella
Stefano
S
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D019295:Computational Biology; D030562:Databases, Protein; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010453:Peptide Synthases / Q000737:chemistry*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase