Homology modeling of milk enzymes using on-line resources: Insights to structure-function and evolutionary relationships

Only 1251 three-dimensional structures for bovine proteins are currently in the protein data bank (PDB), compared with over 60,000 protein sequences, demonstrating a large gap between knowledge of sequences and three-dimensional structures. An alternative approach to obtaining protein structures experimentally is to use homology modelling. In this paper, online homology modelling with Geno3D was used to create structural models for selected milk enzymes, i.e., lysozyme, alkaline phosphatase, lactoperoxidase, lipoprotein lipase, and cathepsin D. Models were also generated for the N-terminal and catalytic domains of plasmin. The models generated were assessed in terms of their geometry, Ramachandran diagrams and root mean-square deviation from targets. Generally, models were plausible and provided a first approach to protein structure for enzymes for which an experimentally determined three-dimensional structure is as yet unavailable. As a positive control, bovine chymosin (which is in the PDB) was modelled on the 38% homologous human protein and the resulting structure shown to be very similar to the experimentally determined crystal structure.