Cellular and retroviral pepsin-like aspartate proteases; This family includes both cellular and retroviral pepsin-like aspartate proteases. The cellular pepsin and pepsin-like enzymes are twice as long as their retroviral counterparts. The cellular pepsin-like aspartic proteases are found in mammals, plants, fungi and bacteria. These well known and extensively characterized enzymes include pepsins, chymosin, rennin, cathepsins, and fungal aspartic proteases. Several have long been known to be medically (rennin, cathepsin D and E, pepsin) or commercially (chymosin) important. The eukaryotic pepsin-like proteases contain two domains possessing similar topological features. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except in the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The eukaryotic pepsin-like proteases have two active site ASP residues with each N- and C-terminal lobe contributing one residue. While the fungal and mammalian pepsins are bilobal proteins, retropepsins function as dimers and the monomer resembles structure of the N- or C-terminal domains of eukaryotic enzyme. The active site motif (Asp-Thr/Ser-Gly-Ser) is conserved between the retroviral and eukaryotic proteases and between the N-and C-terminal of eukaryotic pepsin-like proteases. The retropepsin-like family includes pepsin-like aspartate proteases from retroviruses, retrotransposons and retroelements; as well as eukaryotic DNA-damage-inducible proteins (DDIs), and bacterial aspartate peptidases. Retropepsin is synthesized as part of the POL polyprotein that contains an aspartyl-protease, a reverse transcriptase, RNase H, and an integrase. The POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A) and A2 (retropepsin family).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287   9 NYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIACWIHHKYNSDKSSTYVKNGTSFDIHYGSGSLSGYLS 88
Cdd:cd05490    1 NYMDAQYYGEIGIGTPPQTFTVVFDTGSSNLWVPSVHCSLLDIACWLHHKYNSSKSSTYVKNGTEFAIQYGSGSLSGYLS 80

                 ....*....
gi 407280287  89 QDTVSVPCQ 97
Cdd:cd05490   81 QDTVSIGGL 89

Cathepsin_D2, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of the lysosomal compartment where it functions in protein catabolism. It is a member of the pepsin family of proteinases. This enzyme is distinguished from other members of the pepsin family by two features that are characteristic of lysosomal hydrolases. First, mature Cathepsin D is found predominantly in a two-chain form due to a posttranslational cleavage event. Second, it contains phosphorylated, N-linked oligosaccharides that target the enzyme to lysosomes via mannose-6-phosphate receptors. Cathepsin D preferentially attacks peptide bonds flanked by bulky hydrophobic amino acids and its pH optimum is between pH 2.8 and 4.0. Two active site aspartic acid residues are essential for the catalytic activity of aspartic proteinases. Like other aspartic proteinases, Cathepsin D is a bilobed molecule; the two evolutionary related lobes are mostly made up of beta-sheets and flank a deep active site cleft. Each of the two related lobes contributes one active site aspartic acid residue and contains a single carbohydrate group. Cathepsin D is an essential enzyme. Mice deficient for proteinase cathepsin D, generated by gene targeting, develop normally during the first 2 weeks, stop thriving in the third week and die in a state of anorexia in the fourth week. The mice develop atrophy of ileal mucosa followed by other degradation of intestinal organs. In these knockout mice, lysosomal proteolysis was normal. These results suggest that vital functions of cathepsin D are exerted by limited proteolysis of proteins regulating cell growth and/or tissue homeostasis, while its contribution to bulk proteolysis in lysosomes appears to be non-critical. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287   9 NYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIACWIHHKYNSDKSSTYVKNGTSFDIHYGSGSLSGYLS 88
Cdd:cd05490    1 NYMDAQYYGEIGIGTPPQTFTVVFDTGSSNLWVPSVHCSLLDIACWLHHKYNSSKSSTYVKNGTEFAIQYGSGSLSGYLS 80

                 ....*....
gi 407280287  89 QDTVSVPCQ 97
Cdd:cd05490   81 QDTVSIGGL 89

aspartyl protease; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287   5 EVLKNYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKllDIACWIHHKYNSDKSSTYVKNGTSFD-----IHYG 79
Cdd:PTZ00165 111 QDLLNFHNSQYFGEIQVGTPPKSFVVVFDTGSSNLWIPSKECK--SGGCAPHRKFDPKKSSTYTKLKLGDEsaetyIQYG 188

                         90
                 ....*....|....*
gi 407280287  80 SGSLSGYLSQDTVSV 94
Cdd:PTZ00165 189 TGECVLALGKDTVKI 203

Cathepsin_D2, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of the lysosomal compartment where it functions in protein catabolism. It is a member of the pepsin family of proteinases. This enzyme is distinguished from other members of the pepsin family by two features that are characteristic of lysosomal hydrolases. First, mature Cathepsin D is found predominantly in a two-chain form due to a posttranslational cleavage event. Second, it contains phosphorylated, N-linked oligosaccharides that target the enzyme to lysosomes via mannose-6-phosphate receptors. Cathepsin D preferentially attacks peptide bonds flanked by bulky hydrophobic amino acids and its pH optimum is between pH 2.8 and 4.0. Two active site aspartic acid residues are essential for the catalytic activity of aspartic proteinases. Like other aspartic proteinases, Cathepsin D is a bilobed molecule; the two evolutionary related lobes are mostly made up of beta-sheets and flank a deep active site cleft. Each of the two related lobes contributes one active site aspartic acid residue and contains a single carbohydrate group. Cathepsin D is an essential enzyme. Mice deficient for proteinase cathepsin D, generated by gene targeting, develop normally during the first 2 weeks, stop thriving in the third week and die in a state of anorexia in the fourth week. The mice develop atrophy of ileal mucosa followed by other degradation of intestinal organs. In these knockout mice, lysosomal proteolysis was normal. These results suggest that vital functions of cathepsin D are exerted by limited proteolysis of proteins regulating cell growth and/or tissue homeostasis, while its contribution to bulk proteolysis in lysosomes appears to be non-critical. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287   9 NYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIACWIHHKYNSDKSSTYVKNGTSFDIHYGSGSLSGYLS 88
Cdd:cd05490    1 NYMDAQYYGEIGIGTPPQTFTVVFDTGSSNLWVPSVHCSLLDIACWLHHKYNSSKSSTYVKNGTEFAIQYGSGSLSGYLS 80

                 ....*....
gi 407280287  89 QDTVSVPCQ 97
Cdd:cd05490   81 QDTVSIGGL 89

Cathepsin_D_like, pepsin family of proteinases; Cathepsin D is the major aspartic proteinase of the lysosomal compartment where it functions in protein catabolism. It is a member of the pepsin family of proteinases. This enzyme is distinguished from other members of the pepsin family by two features that are characteristic of lysosomal hydrolases. First, mature Cathepsin D is found predominantly in a two-chain form due to a posttranslational cleavage event. Second, it contains phosphorylated, N-linked oligosaccharides that target the enzyme to lysosomes via mannose-6-phosphate receptors. Cathepsin D preferentially attacks peptide bonds flanked by bulky hydrophobic amino acids and its pH optimum is between pH 2.8 and 4.0. Two active site aspartic acid residues are essential for the catalytic activity of aspartic proteinases. Like other aspartic proteinases, Cathepsin D is a bilobed molecule; the two evolutionary related lobes are mostly made up of beta-sheets and flank a deep active site cleft. Each of the two related lobes contributes one active site aspartic acid residue and contains a single carbohydrate group. Cathepsin D is an essential enzyme. Mice deficient for proteinase cathepsin D, generated by gene targeting, develop normally during the first 2 weeks, stop thriving in the third week and die in a state of anorexia in the fourth week. The mice develop atrophy of ileal mucosa followed by other degradation of intestinal organs. In these knockout mice, lysosomal proteolysis was normal. These results suggest that vital functions of cathepsin D are exerted by limited proteolysis of proteins regulating cell growth and/or tissue homeostasis, while its contribution to bulk proteolysis in lysosomes appears to be non-critical. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287   4 PEVLKNYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIACWIHHKYNSDKSSTYVKNGTSFDIHYGSGSL 83
Cdd:cd05485    1 PEPLSNYMDAQYYGVITIGTPPQSFKVVFDTGSSNLWVPSKKCSWTNIACLLHNKYDSTKSSTYKKNGTEFAIQYGSGSL 80

                         90
                 ....*....|.
gi 407280287  84 SGYLSQDTVSV 94
Cdd:cd05485   81 SGFLSTDTVSV 91

Renin stimulates production of angiotensin and thus affects blood pressure; Renin, also known as angiotensinogenase, is a circulating enzyme that participates in the renin-angiotensin system that mediates extracellular volume, arterial vasoconstriction, and consequently mean arterial blood pressure. The enzyme is secreted by the kidneys from specialized juxtaglomerular cells in response to decreases in glomerular filtration rate (a consequence of low blood volume), diminished filtered sodium chloride and sympathetic nervous system innervation. The enzyme circulates in the blood stream and hydrolyzes angiotensinogen secreted from the liver into the peptide angiotensin I. Angiotensin I is further cleaved in the lungs by endothelial bound angiotensin converting enzyme (ACE) into angiotensin II, the final active peptide. Renin is a member of the aspartic protease family. Structurally, aspartic proteases are bilobal enzymes, each lobe contributing a catalytic Aspartate residue, with an extended active site cleft localized between the two lobes of the molecule. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbor hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287   7 LKNYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIACWIHHKYNSDKSSTYVKNGTSFDIHYGSGSLSGY 86
Cdd:cd05487    1 LTNYLDTQYYGEIGIGTPPQTFKVVFDTGSSNLWVPSSKCSPLYTACVTHNLYDASDSSTYKENGTEFTIHYASGTVKGF 80

                 ....*...
gi 407280287  87 LSQDTVSV 94
Cdd:cd05487   81 LSQDIVTV 88

Eukaryotic aspartyl protease; Aspartyl (acid) proteases include pepsins, cathepsins, and renins. Two-domain structure, probably arising from ancestral duplication. This family does not include the retroviral nor retrotransposon proteases (pfam00077), which are much smaller and appear to be homologous to a single domain of the eukaryotic asp proteases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287   14 QYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKlLDIACWIHHKYNSDKSSTYVKNGTSFDIHYGSGSLSGYLSQDTVS 93
Cdd:pfam00026   1 EYFGTISIGTPPQKFTVIFDTGSSDLWVPSSYCT-KSSACKSHGTFDPSSSSTYKLNGTTFSISYGDGSASGFLGQDTVT 79

                  .
gi 407280287   94 V 94
Cdd:pfam00026  80 V 80

Cellular and retroviral pepsin-like aspartate proteases; This family includes both cellular and retroviral pepsin-like aspartate proteases. The cellular pepsin and pepsin-like enzymes are twice as long as their retroviral counterparts. The cellular pepsin-like aspartic proteases are found in mammals, plants, fungi and bacteria. These well known and extensively characterized enzymes include pepsins, chymosin, rennin, cathepsins, and fungal aspartic proteases. Several have long been known to be medically (rennin, cathepsin D and E, pepsin) or commercially (chymosin) important. The eukaryotic pepsin-like proteases contain two domains possessing similar topological features. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except in the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The eukaryotic pepsin-like proteases have two active site ASP residues with each N- and C-terminal lobe contributing one residue. While the fungal and mammalian pepsins are bilobal proteins, retropepsins function as dimers and the monomer resembles structure of the N- or C-terminal domains of eukaryotic enzyme. The active site motif (Asp-Thr/Ser-Gly-Ser) is conserved between the retroviral and eukaryotic proteases and between the N-and C-terminal of eukaryotic pepsin-like proteases. The retropepsin-like family includes pepsin-like aspartate proteases from retroviruses, retrotransposons and retroelements; as well as eukaryotic DNA-damage-inducible proteins (DDIs), and bacterial aspartate peptidases. Retropepsin is synthesized as part of the POL polyprotein that contains an aspartyl-protease, a reverse transcriptase, RNase H, and an integrase. The POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A) and A2 (retropepsin family).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 407280287  17 GEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIACWiHHKYNSDKSSTYVKNGTSFDIHYGSGSLSGYLSQDTVSVP 95
Cdd:cd05470    1 IEIGIGTPPQTFNVLLDTGSSNLWVPSVDCQSLAIYSH-SSYDDPSASSTYSDNGCTFSITYGTGSLSGGLSTDTVSIG 78

Cathepsin E, non-lysosomal aspartic protease; Cathepsin E is an intracellular, non-lysosomal aspartic protease expressed in a variety of cells and tissues. The protease has proposed physiological roles in antigen presentation by the MHC class II system, in the biogenesis of the vasoconstrictor peptide endothelin, and in neurodegeneration associated with brain ischemia and aging. Cathepsin E is the only A1 aspartic protease that exists as a homodimer with a disulfide bridge linking the two monomers. Like many other aspartic proteases, it is synthesized as a zymogen which is catalytically inactive towards its natural substrates at neutral pH and which auto-activates in an acidic environment. The overall structure follows the general fold of aspartic proteases of the A1 family, it is composed of two structurally similar beta barrel lobes, each lobe contributing an aspartic acid residue to form a catalytic dyad that acts to cleave the substrate peptide bond. The catalytic Asp residues are contained in an Asp-Thr-Gly-Ser/thr motif in both N- and C-terminal lobes of the enzyme. The aspartic acid residues act together to allow a water molecule to attack the peptide bond. One aspartic acid residue (in its deprotonated form) activates the attacking water molecule, whereas the other aspartic acid residue (in its protonated form) polarizes the peptide carbonyl, increasing its susceptibility to attack. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287  15 YYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCklLDIACWIHHKYNSDKSSTYVKNGTSFDIHYGSGSLSGYLSQDTVSV 94
Cdd:cd05486    1 YFGQISIGTPPQNFTVIFDTGSSNLWVPSIYC--TSQACTKHNRFQPSESSTYVSNGEAFSIQYGTGSLTGIIGIDQVTV 78

plasmepsin 4 (PM4); Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287   7 LKNYMDAQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKllDIACWIHHKYNSDKSSTYVKNGTSFDIHYGSGSLSGY 86
Cdd:PTZ00013 131 LDDVANIMFYGEGEVGDNHQKFMLIFDTGSANLWVPSKKCD--SIGCSIKNLYDSSKSKSYEKDGTKVDITYGSGTVKGF 208

                 ....*...
gi 407280287  87 LSQDTVSV 94
Cdd:PTZ00013 209 FSKDLVTL 216

Aspergillopepsin_like, aspartic proteases of fungal origin; The members of this family are aspartic proteases of fungal origin, including aspergillopepsin, rhizopuspepsin, endothiapepsin, and rodosporapepsin. The various fungal species in this family may be the most economically important genus of fungi. They may serve as virulence factors or as industrial aids. For example, Aspergillopepsin from A. fumigatus is involved in invasive aspergillosis owing to its elastolytic activity and Aspergillopepsins from the mold A. saitoi are used in fermentation industry. Aspartic proteinases are a group of proteolytic enzymes in which the scissile peptide bond is attacked by a nucleophilic water molecule activated by two aspartic residues in a DT(S)G motif at the active site. They have a similar fold composed of two beta-barrel domains. Between the N-terminal and C-terminal domains, each of which contributes one catalytic aspartic residue, there is an extended active-site cleft capable of interacting with multiple residues of a substrate. Although members of the aspartic protease family of enzymes have very similar three-dimensional structures and catalytic mechanisms, each has unique substrate specificity. The members of this family has an optimal acidic pH (5.5) and cleaves protein substrates with similar specificity to that of porcine pepsin A, preferring hydrophobic residues at P1 and P1' in the cleave site. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287  15 YYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKLLDIAcwIHHKYNSDKSSTY-VKNGTSFDIHYGSGS-LSGYLSQDTV 92
Cdd:cd06097    1 YLTPVKIGTPPQTLNLDLDTGSSDLWVFSSETPAAQQG--GHKLYDPSKSSTAkLLPGATWSISYGDGSsASGIVYTDTV 78

                 ..
gi 407280287  93 SV 94
Cdd:cd06097   79 SI 80

SAPs, pepsin-like proteinases secreted from pathogens to degrade host proteins; SAPs (Secreted aspartic proteinases) are secreted from a group of pathogenic fungi, predominantly Candida species. They are secreted from the pathogen to degrade host proteins. SAP is one of the most significant extracellular hydrolytic enzymes produced by C. albicans. SAP proteins, encoded by a family of 10 SAP genes. All 10 SAP genes of C. albicans encode preproenzymes, approximately 60 amino acid longer than the mature enzyme, which are processed when transported via the secretory pathway. The mature enzymes contain sequence motifs typical for all aspartyl proteinases, including the two conserved aspartate residues other active site and conserved cysteine residues implicated in the maintenance of the three-dimensional structure. Most Sap proteins contain putative N-glycosylation sites, but it remains to be determined which Sap proteins are glycosylated. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA). The overall structure of Sap protein conforms to the classical aspartic proteinase fold typified by pepsin. SAP is a bilobal enzyme, each lobe contributing a catalytic Asp residue, with an extended active site cleft localized between the two lobes of the molecule. One lobe may be evolved from the other through ancient gene-duplication event. More recently evolved enzymes have similar three-dimensional structures, however their amino acid sequences are more divergent except for the conserved catalytic site motif. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287  15 YYGEIGIGTPPQCFTVVFDTGSSNLWVPsihcklldiacwihhkynsdksstyvkngtSFDIHYGSGS-LSGYLSQDTVS 93
Cdd:cd05474    3 YSAELSVGTPPQKVTVLLDTGSSDLWVP------------------------------DFSISYGDGTsASGTWGTDTVS 52

                 .
gi 407280287  94 V 94
Cdd:cd05474   53 I 53

Plasmepsins are a class of aspartic proteinases produced by the plasmodium parasite; The family contains a group of aspartic proteinases homologous to plasmepsin 5. Plasmepsins are a class of at least 10 enzymes produced by the plasmodium parasite. Through their haemoglobin-degrading activity, they are an important cause of symptoms in malaria sufferers. This family of enzymes is a potential target for anti-malarial drugs. Plasmepsins are aspartic acid proteases, which means their active site contains two aspartic acid residues. These two aspartic acid residue act respectively as proton donor and proton acceptor, catalyzing the hydrolysis of peptide bond in proteins. Aspartic proteinases are composed of two structurally similar beta barrel lobes, each lobe contributing an aspartic acid residue to form a catalytic dyad that acts to cleave the substrate peptide bond. The catalytic Asp residues are contained in an Asp-Thr-Gly-Ser/thr motif in both N- and C-terminal lobes of the enzyme. There are four types of plasmepsins, closely related but varying in the specificity of cleavage site. The name plasmepsin may come from plasmodium (the organism) and pepsin (a common aspartic acid protease with similar molecular structure). This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287  13 AQYYGEIGIGTPPQCFTVVFDTGSSNLWVPSIHCKlldiACWIHHK--YNSDKSSTY----------------VKNGTSF 74
Cdd:cd06096    2 AYYFIDIFIGNPPQKQSLILDTGSSSLSFPCSQCK----NCGIHMEppYNLNNSITSsilycdcnkccyclscLNNKCEY 77

                         90       100
                 ....*....|....*....|..
gi 407280287  75 DIHYGSGS-LSGYLSQDTVSVP 95
Cdd:cd06096   78 SISYSEGSsISGFYFSDFVSFE 99

Chloroplast Nucleoids DNA-binding Protease, catalyzes the degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase; Chloroplast Nucleoids DNA-binding Protease catalyzes the degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in senescent leaves of tobacco. Antisense tobacco with reduced amount of CND41 maintained green leaves and constant protein levels, especially Rubisco. CND41 has DNA-binding as well as aspartic protease activities. The pepsin-like aspartic protease domain is located at the C-terminus of the protein. The enzyme is characterized by having two aspartic protease catalytic site motifs, the Asp-Thr-Gly-Ser in the N-terminal and Asp-Ser-Gly-Ser in the C-terminal region. Aspartic proteases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localized between the two lobes of the molecule. One lobe may be evolved from the other through ancient gene-duplication event. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 407280287  14 QYYGEIGIGTPPQCFTVVFDTGSSNLWVpsiHCKlldiACWIhhkynsdksstyvkngtsFDIHYGSGSLS-GYLSQDTV 92
Cdd:cd05472    1 EYVVTVGLGTPARDQTVIVDTGSDLTWV---QCQ----PCCL------------------YQVSYGDGSYTtGDLATDTL 55

                 .
gi 407280287  93 S 93
Cdd:cd05472   56 T 56