Protein penicillopepsin

The design procedure described above was applied to the protein penicillopepsin, an aspartyl protease from Penicillium janthinellum. The coordinates for the protein were obtained from the Protein Data Bank (Jil) entry 2APP. The crystal structure was determined by James and Sielecki (11) at 1.8A resolution. 

Internal water molecules tend to form clusters. In general, internal water molecules in protein structures are not found isolated but are assembled in clusters. Their hydrogen-bonding scheme could be derived in actinidin (Fig. 19.13), in lysozyme, and in penicillopepsin, based oh the assumption that water molecules act as double donors and acceptors. In some of the protein structures, which have been analyzed in greater detail, an internal water is associated with three acceptor sites indicating three-center bonding as observed in the amino acid zwitterion crystal structures (see Part IB, Chap. 8). 

Hydrogen-bond partners for internal water molecules. In the five proteins lysozyme, carboxypeptidase, cytochrome c, actinidin and penicillopepsin (Table 19.1), the protein groups (numbers in parentheses) which are bonded to internal water molecules are the main-chain C=0 (75), N-H (38), and side-chain atoms... 

Water arrangements essentially similar to those for lysozyme have been found for various other high-resolution structures of proteins, for example, penicillopepsin (James and Sielecki, 1983), ferricytochrome c (Finzel et al., 1985), glyceraldehyde-3-phosphate dehydrogenase (Skar-zynski et al., 1987), and bacteriophage T4 lysozyme (Weaver tuid Matthews, 1987). Wlodawer et al. (1988) described the solvent about phosphate-free ribonuclease A, at 1.26 A, and have compared their results with those for other high-resolution structures of this protein. 

The amino acid compositions vary widely and do not indicate any relationship among the enzymes. However, there is one unusual feature. In four proteins the basic amino acid content is exceptionally low. Human gastricsin and human pepsin have no lysine and contain only one histidine and three arginine residues per molecule. Porcine pepsin has one lysine, one histidine, and two arginine residues. Penicillopepsin has five lysines, three histidines, and no arginine. The significance of this unusual feature, which is not shared by other acid proteases, is not clear. 

---