Aspartic proteinase

The mutation of the hydroxyl group positioned in R-configuration at the C(3) atom of the central statine (rSta) residue of the inhibitor gives rise to AAGbind of -0.51 kcal/mol, which is very close to the experimental value of -0.8 kcal/mol. It may be noted here that the starting configuration of the inhibitor in the enzyme-inhibitor complex is the same as that of pepstatin. The crystal structure of rhizopus pepsin or any other aspartic proteinase... 

B. M. Dunn, Structure and Function of the Aspartic Proteinases Genetics, Structures, and... 

D. Davies, The structure and function of the aspartic proteinases, Annu. Rev. Biophys. 

K. Suguna, E. A. Padlan, C. W. Smith, W. D. Carlson, and D. R. Davies, Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus Chinensis Implications for a mechanism of action, Proc. Natl. Acad. Sci. USA 84 7009 (1987). 

M. N. James, and A. R. Sielecki, Stereochemical analysis of peptide bond hydrolysis catalyzed by the aspartic proteinase penicillopepsin, Biochemistry 24 3701 (1985). 

L. Pearl, and T. Blundell, The active site of aspartic proteinases, FEBS Lett. 174 96... 

BINAP-Ru is effective for the diastereoselective hydrogenation of some chiral yS-keto esters (Fig. 32.13). Reaction of N-Boc-protected (S)-y-amino / -keto esters 13A catalyzed by the (R)-BINAP-Ru complex results in the syn alcohols 13B exclusively [52]. The stereocenter at the / -position is controlled by the chirality of the catalyst therefore, use of the S catalyst affords the anti isomer, as predicted. Derivatives of statine, a key component of the aspartic proteinase inhibitor pep-... 

Scheme 6-28. Statine 65, part of aspartic proteinase inhibitor.

Cynara cardunculus L Cardosin A, an abundant aspartic proteinase, accumulates in protein storage vacuoles Ramalho-Santo et al. (21)... 

K. Guruprasad, V. Dhanaraj, M. Groves, T. L. Blundell, Aspartic Proteinases The Structures and Functions of a Versatile Superfamily of Enzymes , Perspect. Drug Discov. Design 1995, 2, 329-341. 

Based on their sequence homology, disulfide connectivity, and cysteine location within the sequence and chemistry of the reactive site. Pis can be assigned to distinct families, as classified by Laskowski and Kato. Kunitz-type, Bowman—Birk-type, Potato type I and type II, and squash inhibitors are members of these families shown in Table 3. For inhibitors not falling into these classifications more families have been proposed. Pis can also be classified by their target/mode of action. Plants have been found to express Pis that target serine proteinases, cysteine proteinases, aspartic proteinases, and metallo-proteinases. Serine and cysteine protease inhibitors are the best-studied PIs. ... 

Aspartic Proteinases. This group of proteinases is named for the aspartic acid residue in the active site. Previously, this group of enzymes was often referred to as the "acid proteases" (4). Members of this group are generally found only in eukaryotic organisms. However, clear evidence has been presented that certain viruses, most importantly the virus (HIV-1) considered to give rise to autoimmune deficiency disease (AIDS), and the polio virus, contain coding sequences for a dimeric aspartic proteinase which is involved in the... 

The mechanism of the aspartic proteinases involves two essential catalytic aspartate residues. There is some controversy in the literature as to whether the mechanism involves an acyl en me intermediate or an amino enzyme intermediate (4). However, there is no direct evidence for either intermediate so additional studies with inhibitors and pseudosubstrates along with crystallographic analysis will ultimately be required to resolve these questions. 

Renin [2] is an aspartate proteinase (see p. 176). It is formed by the kidneys as a precursor (prorenin), which is proteolytically activated into renin and released into the blood. In the blood plasma, renin acts on angiotensinogen, a plasma glycoprotein in... 

At the center of the apoptotic process lies a group of specialized cysteine-containing aspartate proteinases (see p. 176), known as cas-pases. These mutually activate one another, creating an enzyme cascade resembling the cascade involved in blood coagulation (see... 

This enzyme [EC 3.4.23.34], also known as slow-moving proteinase and erythrocyte membrane aspartic proteinase, is similar to cathepsin D, albeit with a slightly broader specificity. 

This aspartic proteinase [EC 3.4.23.22], from the ascomy-cete Endothia parasitica, catalyzes the hydrolysis of proteins with broad specificity similar to that of pepsin A, with preferential action on substrates containing hydrophobic residues at PI and PI. ... 

This enzyme [EC 3.4.23.19], also known as aspergillopep-sin II, proctase A, and Aspergillus niger var. macrosporus aspartic proteinase, catalyzes the hydrolysis of peptide bonds in proteins. It has been isolated from Aspergillus niger var. macrosporus and is distinct from aspergillopep-sin I in specificity and in insensitivity to pepstatin. 

Most of the EF-hand motifs have one water (—X). On the other hand, in Rhizopus chinensis aspartic proteinase (Suguna et al., 1987) there is one main-chain carbonyl oxygen bound to calcium and six water molecules to complete the pentagonal bipyramidal coordination. Calcium coordination has been measured in several viruses, such as Southern bean mosaic virus (Silva and Rossmann, 1985), satellite tobacco necrosis virus (Jones and Liljas, 1984), and tomato bushy stunt virus IV (Olson et al., 1983). 

Renin is a member of the homologous group of enzymes known as aspartic proteinases that includes pepsin and a group of fungal enzymes such as endothiapepsin, penicillopepsin, and rhizopuspepsin. 

There is no evidence that aspartic proteinase catalysis involves a covalently bound intermediate [11] and major advances in the design of nonhydrolysable analogs have stemmed from attempts to mimic an intermediate of the following form. 

Aspartic proteinase inhibitors in which the scissile bond is replaced by a phosphinic acid group (shown below) have been reported [28]. 

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