Aspartyl Proteinases

Hadzi, D., M. Hodoscek, D. Turk, and V. Harb. 1988. Theoretical Investigations of Structure and Enzymatic Mechanisms of Aspartyl Proteinases Part 2. Ab initio calculations on some possible initial steps of proteolysis, J. Mol. Struct. (Theochem) 181, 71-80. 

T. Hofmann, A. L. Fink, B. M. Dunn, Cryoenzymology of Penicillopepsin with an Appendix Mechanism of Action of Aspartyl Proteinases , Biochemistry 1984, 23, 5247-5256. 

Figure 10.2 Schematic representation of the tertiary structure of an aspartyl proteinase, showing the cleft which contains the active site arrows indicate P structures and cylinders the a-helices (from Foltmann, 1987).

Penicillium caseicolum produces an extracellular aspartyl proteinase and a metalloproteinase with properties very similar to those of the extracellular enzymes produced by P roqueforti (Trieu-Cout and Gripon 1981 Trieu-Cout et al. 1982). Breakdown of casein in mold-ripened cheese results from the synergistic action of rennet and the proteases of lactic streptococci and penicillia (Desmazeaud and Gripon 1977). Peptidases of both lactic acid bacteria and penicillia contribute to formation of free amino acid and nonprotein nitrogen (Gripon et al. 1977). 

Trieu-Cuot, P., Archiere-Haze, M. and Gripon, J. C. 1982. Effect of aspartyl proteinases of Penicillium caseicolum and Penicillium roqueforti on caseins. J. Dairy Res. 49, 487-500. 

Jean, L., Long, M., Young, J., Pery, P. and Tomley, F. (2001) Aspartyl proteinase genes from apicomplexan parasites evidence for evolution of the gene structure. Trends in Parasitology 17, 491 t98. 

During last decades the domains C-2 symmetry (the dyad rotation symmetry) of low-B palindrome was established in many enzymes (chymotrypsin, trypsin, aspartyl proteinases, HIV-1 protease, carboxypeptidase A, phospholipase A-2 ribonuclease, etc.) (Lumry, 2002 and references therein). It is proposed that the pair domain closure causes constrain of pretransition state complex that activates cleavage or formation of chemical bonds. Thus control of strong bonds by the cooperation of many matrix or knots bonds takes place. As an example, in the active site of carboxypeptidase A the zinc ion is attached to one of the catalytic domains by histidine 69 and glutamine 72 and connected by hystidine 196 to the second domain. Similar structures were found in the chymotrypsin and pepsin active sites where protons are driven under compression of the domains closure. 

White TC, Miyasaki SH, Agabian N Three distinct secreted aspartyl proteinases in Candida albicans. JBacteriol 1993 175 6126-6133. 

Naglik JR, Newport G, White TC, Fernandes-Naglik LL, Greenspan JS, Greenspan D, Sweet SP, Challacombe SJ, Agabian N In vivo analysis of secreted aspartyl proteinase expression in human oral Candidiasis. Infect Immun 1999 67 2482-2490. 

Hube B, Sanglard D, Odds FC, Hess D, Monod M, Schafer W, Brown AJP, Gow NAR Disruption of each of the aspartyl proteinase genes SAPl, SAP2, and SAP3 of Candida albicans attenuates virulence. Infect Immun 1997 65 3529-3538. 

Sanglard D, Hube B, Monod M, Odds FC, Gow NAR A triple deletion of the aspartyl proteinase genes SAP4, SAPS, and SAP6 of Candida albicans causes attenuated virulence. Infect Immim 1997 65 3539-3546. 

De Bemardis F, Arancia S, Morelli L, Hube B, Sanglard D, Schafer W, Cassone A Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2, are virulence factors for Candida vaginitis. J Infect Dis 1999 179 201-208. 

Korting HC, Schaller M, Eder G, Hamm G, Bohmer U, Hube B Effects of the human immunodeficiency vims (HIV) proteinase inhibitors Saquinavir and Indinavir on in vitro activities of secreted aspartyl proteinases of Candida albicans isolates from HIV-infected patients. Antimicrob Agents Chemother 1999 43 2038-2042. 

Hube B, Monod M, Schofield A, Brown AJP, Gow NAR Ejq>ression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans. Mol Microbiol 1994 14 ... 

White TC, Agabian N Candida albicans secreted aspartyl proteinases Isoenzyme pattern is determined by cell type, and levels are determined by environmental factors. J Bacteriol 1995 177 ... 

Inhibitors of HIV-1 protease, agents that capitalize on a small difference in the virion and mammalian aspartyl proteinase, offer potential chemotherapeutic benefit. Clinically available agents include saquinavir, ritinavir and indinavir. See PROTEASE INHIBITORS. 

Laurent, F., Bourdieu, C., Kaga, M. et al (1993) Cloning and characterization of an Eimeria acervulina sporozoite gene homologous to aspartyl proteinases. Mol Biochem. Parasitol 62 303-312. 

Chymosin (EC 3.4.23.4), the principal proteinase in traditional rennets used for cheesemaking (Rothe et al., 1977), is an aspartyl proteinase of gastric origin, secreted by young mammals. The principal role of chymosin in cheesemaking is to coagulate the milk. However, about 6% of the chymosin added to cheese milk is retained in the curd for Cheddar and plays a... 

S. Gottschalk, A. Waheed, B. Schmidt, P. Laidler, and K. von Figura, Sequential processing of lysosomal acid phosphatase by a cytoplasmic fliiol proteinase and a lysosomal aspartyl proteinase, EMBO J, 8 (1989) 3215-3219. 

Aspartyl proteinase containing 340 AA residues. Prod, by kidney, also found in amniotic fluid. Converts angiotensinogenin to angiotensin I. 

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