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PubMed1987

Modulation of Pea Membrane beta-Glucan Synthase Activity by Calcium, Polycation, Endogenous Protease, and Protease Inhibitor.

beta-Glucan synthase activity in plant membranes can be markedly altered by a multiplicity of apparently unrelated factors. In pea epicotyl membranes it is enhanced by low and inhibited by high concentrations of added Ca(2+), trypsin or soluble pea protease. Ca(2+) stimulates preexisting synthase activity, particularly in the presence of polycations (spermidine), but protease treatments activate and, with time, inactivate synthase zymogen. Endogenous pea protease activity is also associated with washed pea membrane and appears to be responsible for the decay observed with time in the beta-glucan synthase activity. Endogenous pea protease activity is inhibited by thiol inhibitors, e.g. iodoacetamide and Hg(2+), and by a heat-stable peptide, molecular weight approximately 10,000, that is found in supernatants of pea extracts. These protease inhibitors have the capacity to protect beta-glucan synthase activity from denaturation or its zymogen from activation due to endogenous or added protease activity. Evidence is described which supports the proposal that 1,4-beta-glucan synthase is destroyed and possibly converted to 1,3-beta-glucan synthase activity by protease action, and that the latter may then be greatly enhanced by Ca(2+) and polycations.

Journal Article↗
PubMed2004

Double-stranded DNA bacteriophage prohead protease is homologous to herpesvirus protease.

Double-stranded DNA bacteriophages and herpesviruses assemble their heads in a similar fashion; a pre-formed precursor called a prohead or procapsid undergoes a conformational transition to give rise to a mature head or capsid. A virus-encoded prohead or procapsid protease is often required in this maturation process. Through computational analysis, we infer homology between bacteriophage prohead proteases (MEROPS families U9 and U35) and herpesvirus protease (MEROPS family S21), and unify them into a procapsid protease superfamily. We also extend this superfamily to include an uncharacterized cluster of orthologs (COG3566) and many other phage or bacteria-encoded hypothetical proteins. On the basis of this homology and the herpesvirus protease structure and catalytic mechanism, we predict that bacteriophage prohead proteases adopt the herpesvirus protease fold and exploit a conserved Ser and His residue pair in catalysis. Our study provides further support for the proposed evolutionary link between dsDNA bacteriophages and herpesviruses.

Amino Acid Sequence↗
PubMed2002

Novel chromaffin granule serpins, endopin 1 and endopin 2: endogenous protease inhibitors with distinct target protease specificities.

Endopin 1 and endopin 2 represent two novel serpin protease inhibitors localized within chromaffin granules, secretory vesicles of adrenomedullary chromaffin cells that represent a model neuroendocrine cell for synthesis and secretion of peptide neurotransmitters. This chapter describes the molecular features of the primary sequences of endopin 1 and endopin 2 that provided prediction of their distinct target protease specificities. Endopin 1 inhibits trypsin that cleaves at basic residues. In contrast, endopin 2 possesses cross-class inhibition of papain and elastase that represent cysteine and serine proteases, respectively. Cell biological studies indicate that endopin 1 and endopin 2 are localized within chromaffin granules. These results implicate endopin 1 inhibition in vivo of trypsin-like proteases in secretory vesicles, and endopin 2 inhibition of papain- or elastase-like proteases. Indeed, endopin 2 inhibits the endogenous cysteine protease PTP (prohormone thiol protease), present in chromaffin granules, that participates in the proteolytic processing of proenkephalin. These findings indicate the presence of endogenous endopin 1 and endopin 2 in secretory vesicle function.

Amino Acid Sequence↗
PubMed1989

Inactivation of human gamma interferon by Pseudomonas aeruginosa proteases: elastase augments the effects of alkaline protease despite the presence of alpha 2-macroglobulin.

Pseudomonas aeruginosa alkaline protease (AP) has recently been shown to produce limited proteolysis of human gamma interferon (IFN-gamma) and thereby destroy the antiviral and macrophage-activating activities of the lymphokine. In the present study we describe some of the characteristics of Pseudomonas elastase (E) with regard to inactivation of human IFN-gamma. The inhibitory effect of E on IFN-gamma bioactivity differed from that of AP in that the direct effects of E were reduced in the presence of human serum. That this property of human serum was in large part attributable to the protease inhibitor alpha 2-macroglobulin (alpha 2-M) was suggested by the following observations: (i) methylamine treatment of serum reduced its effect on E, (ii) E interacted directly with alpha 2-M to induce a characteristic conformational change in the protease inhibitor, and (iii) preformed E-alpha 2-M complexes lacked IFN-gamma-degrading activity. Despite these findings, anti-E antiserum partially neutralized the effect that a Pseudomonas filtrate showed on IFN-gamma, suggesting that E contributes to the activity of bacterial filtrates. Treatment of IFN-gamma with E in the presence of a suboptimal concentration of AP resulted in an E dose-dependent inactivation of the lymphokine. Preformed E-alpha 2-M complexes, although ineffective by themselves at cleaving IFN-gamma, degraded the lymphokine, providing AP was also present in the reaction mixture. These data demonstrate that the destruction of small, biologically significant peptides by Pseudomonas proteases can involve protease-protease synergy that acts even in the presence of the serum protease inhibitor alpha 2-M.

Endopeptidases↗
PubMed1971

Regulation of extracellular protease production in Bacillus cereus T: characterization of mutants producing altered amounts of protease.

Twenty-nine mutants of Bacillus cereus T were selected on casein agar for their inability to produce large amounts of extracellular protease. They all formed spores, and 27 were also auxotrophs for purines or pyrimidines. Upon reversion to prototrophy, a large fraction regained the capacity to produce protease. Conversely, reversion to normal protease production resulted in loss of the purine or pyrimidine requirement in a large fraction of the revertants. One spontaneous low-protease-producing pyrimidine auxotroph studied in detail grew as well as the wild type and produced spores which were identical to those produced by the wild type on the basis of heat resistance, dipicolinic acid content, density, and appearance in the electron microscope. The rate of protein turnover in the mutant was the same as the wild type. The mutant did grow poorly, however, when casein was the principal carbon source. A mutant excreting 5 to 10 times as much protease as the wild type was isolated as a secondary mutation from the hypoproducer discussed above. Loss of the pyrimidine requirement in this case did not alter the regulation of protease production. Although the secondary mutant grew somewhat faster in most media than the wild type, the final cell yield was lower. The spores of this mutant appeared to have excess coat on the basis of both electron microscopic and chemical studies. There appear to be closely related but distinct catabolic controls for both extracellular protease and spore formation. These controls can be dissociated as for the hypoproducers but can also appear integrated as for the hyperprotease producer.

Agar↗
PubMed1991

Cloning and expression in Escherichia coli of the Serratia marcescens metalloprotease gene: secretion of the protease from E. coli in the presence of the Erwinia chrysanthemi protease secretion functions.

The Serratia marcescens extracellular protease SM is secreted by a signal peptide-independent pathway. When the prtSM gene was cloned and expressed in Escherichia coli, the cells did not secrete protease SM. The lack of secretion could be very efficiently complemented by the Erwinia chrysanthemi protease B secretion apparatus constituted by the PrtD, PrtE, and PrtF proteins. As with protease B and alpha-hemolysin, the secretion signal was located within the last 80 amino acids of the protease. These results indicate that the mechanism of S. marcescens protease SM secretion is analogous to the mechanisms of protease B and hemolysin secretion.

Blotting, Western↗
PubMed2001

HreP, an in vivo-expressed protease of Yersinia enterocolitica, is a new member of the family of subtilisin/kexin-like proteases.

The role of proteases in pathogenesis is well established for several microorganisms but has not been described for Yersinia enterocolitica. Previously, we identified a gene, hreP, which showed significant similarity to proteases in a screen for chromosomal genes of Y. enterocolitica that were exclusively expressed during an infection of mice. We cloned this gene by chromosome capture and subsequently determined its nucleotide sequence. Like inv, the gene encoding the invasin protein of Y. enterocolitica, hreP is located in a cluster of flagellum biosynthesis and chemotaxis genes. The genomic organization of this chromosomal region is different in Escherichia coli, Salmonella, and Yersinia pestis than in Y. enterocolitica. Analysis of the distribution of hreP between different Yersinia isolates and the relatively low G+C content of the gene suggests acquisition by horizontal gene transfer. Sequence analysis also revealed that HreP belongs to a family of eukaryotic subtilisin/kexin-like proteases. Together with the calcium-dependent protease PrcA of Anabaena variabilis, HreP forms a new subfamily of bacterial subtilisin/kexin-like proteases which might have originated from a common eukaryotic ancestor. Like other proteases of this family, HreP is expressed with an N-terminal prosequence. Expression of an HreP-His(6) tag fusion protein in E. coli revealed that HreP undergoes autocatalytic processing at a consensus cleavage site of subtilisin/kexin-like proteases, thereby releasing the proprotein.

Amino Acid Sequence↗
PubMed1991

N-terminal truncation of the scrapie-associated form of PrP by lysosomal protease(s): implications regarding the site of conversion of PrP to the protease-resistant state.

Scrapie and related transmissible spongiform encephalopathies result in the accumulation of a protease-resistant form of an endogenous brain protein called PrP. As an approach to understanding the scrapie-associated modification of PrP, we have studied the processing and sedimentation properties of protease-resistant PrP (PrP-res) in scrapie-infected mouse neuroblastoma cells. Like brain-derived PrP-res, the neuroblastoma cell PrP-res aggregated in detergent lysates, providing evidence that the tendency to aggregate is an intrinsic property of PrP-res and not merely a secondary consequence of degenerative brain pathology. The PrP-res species had lower apparent molecular masses than the normal, protease-sensitive PrP species and were not affected by moderate treatments with proteinase K. This suggested that the PrP-res species were partially proteolyzed by the neuroblastoma cells. Immunoblot analysis of PrP-res with a panel of monospecific anti-PrP peptide sera confirmed that the PrP-res species were quantitatively truncated at the N terminus. The metabolic labeling of PrP-res in serum-free medium did not prevent the proteolysis of PrP-res, showing that the protease(s) involved was cellular rather than serum-derived. The PrP-res truncation was inhibited in intact cells by leupeptin and NH4Cl. This provided evidence that a lysosomal protease(s) was involved, and therefore, that PrP-res was translocated to lysosomes. When considered with other studies, these results imply that the conversion of PrP to the protease-resistant state occurs in the plasma membrane or along an endocytic pathway before PrP-res is exposed to endosomal and lysosomal proteases.

Animals↗
PubMed2004

A protease activated receptor-2 (PAR-2) activating peptide, tc-LIGRLO-NH2, induces protease release from mast cells: role in TNF degradation.

BACKGROUND: Mast cell (MC)-derived serine proteases have been implicated in a variety of inflammatory processes. We have previously shown that rat peritoneal MC (PMC) express mRNA for protease activated receptor 2 (PAR-2), a G-coupled receptor activated by trypsin-like proteases. Recent evidence also suggests that MC-induced inflammation can be mediated through PAR. Therefore, we hypothesized that specific PAR-2 agonist peptides (PAR-2ap) induce protease release from PMC. RESULTS: Western blot analysis of PMC supernatants revealed that a PAR-2ap, tc-LIGRLO (10 microM), stimulated the release of rat MC protease (RMCP)-1, RMCP-5 and carboxypeptidase-A. The release was evident by 20 min but further increased up to 8 h. To study the biological effects of protease release we tested supernatants from tc-LIGRLO, tc-OLRGIL (inactive control peptide) and antigen-activated PMC for proteolytic activity by seeding with TNF (150 pg/ml), incubating for 8 h at 37 degrees C, and measuring TNF remaining in the supernatants. Supernatants from tc-LIGRLO-stimulated PMC degraded 44 % of seeded TNF (n = 5). Moreover, this TNF proteolysis was dependent on the concentration of tc-LIGRLO used to stimulate PMC, and was significantly inhibited (94 %) by soybean trypsin inhibitor. Antigen and tc-OLRGIL induced no significant release of such proteolytic activity. CONCLUSIONS: These data indicate that a PAR-2ap induces the release of proteases from mast cells, which may degrade extracellular cytokines and other substrates thus modulating the inflammatory response.

Animals↗
PubMed1990

Site-directed mutagenesis suggests close functional relationship between a human rhinovirus 3C cysteine protease and cellular trypsin-like serine proteases.

Human rhinoviruses, like other picornaviruses, encode a cysteine protease (designated 3C) which cleaves mainly at viral Gln-Gly pairs. There are significant areas of homology between picornavirus 3C cysteine proteases and cellular serine proteases (e.g. trypsin), suggesting a functional relationship between their catalytic regions. To test this functional relationship, we made single substitutions in human rhinovirus type 14 protease 3C at seven amino acid positions which are highly conserved in the 3C proteases of animal picornaviruses. Substitutions at either His-40, Asp-85, or Cys-146, equivalent to the trypsin catalytic triad His-57, Asp-102, and Ser-195, respectively, completely abolished 3C proteolytic activity. Single substitutions were also made at either Thr-141, Gly-158, His-160, or Gly-162, which are equivalent to the trypsin specificity pocket region. Only the mutant with a conservative Thr-141 to Ser substitution exhibited proteolytic activity, which was much reduced compared with the parent. These results, together with immunoprecipitation data which indicate that Asp-85, Thr-141, and Cys-146 lie in accessible surface regions, suggest that the catalytic mechanism of picornavirus 3C cysteine proteases is closely related to that of cellular trypsin-like serine proteases.

Amino Acid Sequence↗
PubMed1983

Conformation and protease binding activity of binary and ternary human alpha 2-macroglobulin-protease complexes.

Human alpha 2-macroglobulin (alpha 2M) undergoes a conformational change after reaction with proteases. In this report, it is shown that although two trypsin molecules may bind simultaneously to each alpha 2M, only one trypsin is necessary to induce alpha 2M conformational change. Ternary complexes of alpha 2M and either two radioiodinated trypsins or two nonradioiodinated trypsins were purified by gel filtration chromatography. The nonradioactive complex did not bind 125I-trypsin, even after incubation for 24 h with the free protease present at a large molar excess. Under comparable conditions, a large molar excess of nonradioactive trypsin did not cause significant dissociation of the complex prepared with radioiodinated protease. Equations are presented that distinguish between two separate models of protease binding and demonstrate that binary alpha 2M-trypsin complex retains no significant trypsin binding activity despite the presence of a vacant protease binding site. Purified alpha 2M-plasmin complex, with 1.10 mol of plasmin/mol of inhibitor, also retained no trypsin binding activity as assessed with radioiodinated protein binding experiments. These studies suggest that reactions of alpha 2M with proteases are accurately described by the "trap hypothesis" (Barrett, A. J., and Starkey, P. M. (1973) Biochem. J. 133, 709-724) independent of protease size or binding stoichiometry.

Fibrinolysin↗
PubMed1993

Cancer-associated SCM-recognition, immunedefense suppression, and serine protease protection peptide. Part III. CRISPP peptide protection of serine proteases against inhibition.

The cancer SCM-recognition, immunedefense suppression, and serine protease protection (CRISPP) peptide, produced by cancer cells, is homologous to the Pn', enzyme-baiting region of the serine protease inhibitor alpha 1-PI. In contrast to the inhibitory function of the intact alpha 1-PI, the CRISPP peptide protects cancer-associated serine proteases against inhibition by alpha 1-PI. In the presence of alpha 1-PI, the prevention of inhibition is a competitive, concentration-dependent process. The shortest fragment of the 29 amino acid sequence of the synthetic, CRISPPs peptide, which protects serine proteases against inhibition as efficiently as the whole molecule, encompasses the amino terminal amino acid residues 1 to 7. Serine proteases and their inhibitor, alpha 1-PI, are involved in the control of many intra- and extracellular physiological processes, including degradative actions in cancer cell invasion, metastatic spread, and neovascularization of tumors. The CRISPP peptide protection of serine proteases against inhibition could unbalance the regulatory controls requiring limited proteolysis by serine proteases. The inherited and/or acquired aberrations resulting in the production of CRISPP peptides in cancer cells could, therefore, be one of the key factors involved in the carcinogenic transformation, enhancing uncontrolled gene derepression and DNA synthesis, and supporting invasion and metastasis. A hypothesis on the mechanism of CRISPP peptide action is proposed.

Epitopes↗
PubMed1994

Characterization of the serine protease and serine protease inhibitor from the tissue-penetrating nematode Anisakis simplex.

A serine protease and a serine protease inhibitor were purified from infective larvae of the parasitic nematode Anisakis simplex. The serine protease was found to be trypsin-like and preferentially cleaved substrates with the basic amino acid arginine at the P1 position (Z-Gly-Pro-Arg-AMC (where Z is benzyloxycarbonyl), Km = 0.019 mM, and Z-Phe-Pro-Arg-AMC, Km = 0.013 mM) at rates similar to those determined for trypsin (0.002 mM and 0.006 mM, respectively). However, the presence of a bulky hydrophobic residue at the P2 position (Z-Phe-Arg-AMC, Km = 13.3 mM, and Z-Ile-Leu-Val-Arg-AMC, Km = 24.7 mM) greatly decreased the rate of substrate hydrolysis. Internal amino acid sequence information was obtained from three endo Lys-C digestion fragments of the purified enzyme. These sequences were > 89% (33:37) identical with that of porcine trypsin. A second serine protease 85% (11:13) identical with that of a secreted tissue-destructive serine protease from the pathogenic bacterium Dichelobacter nodosus was also identified. The serine protease inhibitor was found to inhibit trypsin, elastase, and the Anisakis serine protease stoichiometrically, but did not inhibit chymotrypsin. The amino acid sequence of the amino terminus as well as two internal endo Lys-C fragments were determined. Approximately 96% (47:49) of the residues were identical with soybean trypsin inhibitor, indicating that this inhibitor belongs to the Kunitz-type family of inhibitors.

Amino Acid Sequence↗
PubMed1994

Identification of three catalytic triad constituents and Asp-225 essential for function of lysine-specific serine protease, Achromobacter protease I.

Achromobacter protease I is a lysine-specific serine protease that Achromobacter lyticus M497-1 extracellularly secretes. The structural aspects necessary for the protease to function were investigated by means of site-directed mutagenesis to identify the constituents of the catalytic triad and the amino acid residue responsible for lysine specificity. The precursor molecules, which were produced by substitution of His-57, Asp-113, or Ser-194 for alanine, could not be converted to the mature form. In contrast, a precursor of a mutant in which either His-56 or Ser-193 is converted to alanine was perfectly processed autocatalytically and attained full protease activity. Substitution of Glu-190, one of the two candidates for determining lysine specificity, to glutamine, aspartic acid, or leucine had no or little effect on both proteolytic activity and substrate specificity. However, the kinetic parameters were subtly different from one another, depending on the nature of substituents in these mutants. The substitution of the other candidate, Asp-225, for asparagine or leucine resulted in the failure of maturation to the active forms. However, the precursor of the D225E mutant slowly matured and was essentially inactive. The observed reduction of protease activity is largely due to a decrease in the affinity of lysine to the protease. These results suggest that His-57, Asp-113, and Ser-194 are the three constituents of the catalytic triad in Achromobacter protease I and that Asp-225 plays a critical role in restricted substrate specificity as a lysyl endopeptidase.

Alcaligenes↗
PubMed1996

Conserved structure and adjacent location of the thrombin receptor and protease-activated receptor 2 genes define a protease-activated receptor gene cluster.

BACKGROUND: Thrombin is a serine protease that elicits a variety of cellular responses. Molecular cloning of a thrombin receptor revealed a G protein-coupled receptor that is activated by a novel proteolytic mechanism. Recently, a second protease-activated receptor was discovered and dubbed PAR2. PAR2 is highly related to the thrombin receptor by sequence and, like the thrombin receptor, is activated by cleavage of its amino terminal exodomain. Also like the thrombin receptor, PAR2 can be activated by the hexapeptide corresponding to its tethered ligand sequence independent of receptor cleavage. Thus, functionally, the thrombin receptor and PAR2 constitute a fledgling receptor family that shares a novel proteolytic activation mechanism. To further explore the relatedness of the two known protease-activated receptors and to examine the possibility that a protease-activated gene cluster might exist, we have compared the structure and chromosomal locations of the thrombin receptor and PAR2 genes. MATERIALS AND METHODS: The genomic structures of the two protease-activated receptor genes were determined by analysis of lambda phage, P1 bacteriophage, and bacterial artificial chromosome (BAC) genomic clones. Chromosomal location was determined with fluorescent in situ hybridization (FISH) on metaphase chromosomes, and the relative distance separating the two genes was evaluated both by means of two-color FISH and analysis of YACs and BACs containing both genes. RESULTS: Analysis of genomic clones revealed that the two protease-activated receptor genes share a two-exon genomic structure in which the first exon encodes 5'-untranslated sequence and signal peptide, and the second exon encodes the mature receptor protein and 3'-untranslated sequence. The two receptor genes also share a common locus with the two human genes located at 5q13 and the two mouse genes at 13D2, a syntenic region of the mouse genome. These techniques also suggest that the physical distance separating these two genes is less than 100 kb. CONCLUSIONS: The fact that the thrombin receptor and PAR2 genes share an identical structure and are located within approximately 100 kb of each other in the genome demonstrates that these genes arose from a gene duplication event. These results define a new protease-activated receptor gene cluster in which new family members may be found.

Amino Acid Sequence↗
PubMed1992

An ultrasensitive human immunodeficiency virus type 1 protease radioimmuno rate assay with a potential for monitoring blood levels of protease inhibitors in acquired immunodeficiency disease syndrome patients.

The angiotensin I-based peptide Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu-Glu-Ser yields angiotensin I (Ang I) and Leu-Glu-Glu-Ser upon hydrolysis by the human immunodeficiency virus type 1 (HIV-1) protease, but not by human renin. N-terminal sequencing of the reaction products showed that the HIV-1 protease cleaved exclusively at the Leu-Leu bond. The rate of Ang I formation can be measured by a radioimmunoassay, since the parent peptide has minimal cross reactivity in this assay. The rate of enzymatic hydrolysis is maximal at pH 4.5-5.0 and at an ionic strength of 1 M. At 37 degrees C, 0.1 M Na acetate buffer, pH 5.0, 1 M NaCl, 10% glycerol, 5% ethylene glycol, 1 mg/ml bovine serum albumin, and 3 mM EDTA, the reaction obeys Michaelis-Menten type kinetics with Km = 17.2 +/- 3.5 microM and kcat = 2.30 +/- 0.33 min-1. The activity assay readily quantitates as little as 0.25 nM of HIV-1 protease. The production of Ang I by the HIV-1 protease is inhibited in the presence of a HIV-1 protease inhibitor. The newly discovered substrate is relatively insensitive to human or monkey serum. Therefore, the effect of sera from 20 patients with advanced acquired immunodeficiency disease syndrome (AIDS) on Ang I production in the above assay system was examined. Results of this study indicate that it may be possible to adapt the above Ang I-based system to determine blood levels of HIV-1 protease inhibitors in AIDS patients during clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Co-distribution of protease nexin-1 and protease nexin-2 in brains of non-human primates.

The protease nexins are protease inhibitors which regulate key blood coagulation proteases and which appear to be involved in certain physiological and pathological processes in the brain. Protease nexin-1 (PN-1), a potent inhibitor of thrombin, can regulate processes on cultured neurons and astrocytes. Protease nexin-2 (PN-2), a potent inhibitor of coagulation factor XIa, is identical to the secreted form of the Alzheimer's amyloid beta-protein precursor. In the present studies, PN-1 and PN-2 were analyzed in different tissues of monkey using monoclonal antibodies for either quantitative immunoblotting or specific [125I]protease-binding assays. PN-1 was detected only in brain. PN-2 was most abundant in brain, followed by testis and to a lesser extent kidney. Other tissues examined including spinal cord, heart, pancreas, spleen, liver, lung and muscle were essentially devoid of both PN-1 and PN-2. Within the brain, the levels of PN-1 and PN-2 were highest in the parietal cortex and lowest in the cerebellum and brainstem. The thalamus and striatum contained intermediate amounts of both proteins. Aged Cebus monkey cerebral cortical tissue contained slightly lower levels of PN-1 than did the middle-aged or young monkey tissue. The co-distribution of PN-1 and PN-2 in brain, their relative abundance in brain cortex, and previous studies on their functions suggest that in the brain they may participate in the regulation of blood coagulation and cell growth and differentiation.

Amyloid beta-Protein Precursor↗
PubMed1990

Comparison of inhibitor binding in HIV-1 protease and in non-viral aspartic proteases: the role of the flap.

The crystal structure of HIV-1 protease with an inhibitor has been compared with the structures of non-viral aspartic proteases complexed with inhibitors. In the dimeric HIV-1 protease, two 4-stranded beta-sheets are formed by half of the inhibitor, residues 27-29, and the flap from each monomer. In the monomeric non-viral enzyme the single flap does not form a beta-sheet with an inhibitor. The HIV-1 protease shows more interactions with a longer peptide inhibitor than are observed in non-viral aspartic protease-inhibitor complexes. This, and the large movement of the flaps, restricts the conformation of the protease cleavage sites in the retroviral polyprotein precursor.

Aspartic Acid Endopeptidases↗