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Biomedical subjects

S Iwanaga

Publications and source records attributed to S Iwanaga.

At least 91 records · Page 5Linked to original sources
PubMed1996

Clotting and immune defense in Limulidae.

The blue blood of the horseshoe crab contains a sophisticated defense system very sensitive to pathogens or foreign materials. The hemocytes circulating in the hemolymph detect trace amounts of LPS molecules on the invading microorganisms and respond quickly to release the granular components into the external milieu. The coagulation system composed of three serine protease zymogens, factor C, factor B, and proclotting enzyme, and a clottable protein, coagulogen, is activated by LPS to form insoluble coagulin gel. The coagulation system also responds to beta-(1,3) glucan through the activation of unique heterodimeric serine protease zymogen, factor G. The pathogens are, thus, engulfed in the gel and subsequently killed by antimicrobial substances with various specificities, which are also released from cells. The horseshoe crab has developed two kinds of serine protease zymogens as biological sensors, factor C and factor G, which are responsive to LPS and beta-(1,3) glucan on the surface of Gram-negative bacteria and fungi, respectively. These are possible invaders for horseshoe crabs and also for most animals including humans. This novel heterodimeric serine protease zymogen, factor G, may open a new way to develop an innovative assay system to quantitate beta-(1,3) glucans. Furthermore, these LPS and beta-(1,3) glucan sensitive factors could be utilized as a unique tool to analyze other biological reactions caused by LPS or the glucan. Although the coagulation reaction in horseshoe crabs is famous, it is not the only defense mechanism of this animal. Many agglutinins are present either in hemolymph plasma or in the cell. The hemolymph plasma also has cytolytic activity against foreign cells. These cellular and humoral defense systems, in concert, defend themselves from invading foreign organisms. Such a sophisticated defense system has allowed the horseshoe crab to survive for more than 200 million years on the earth. Horseshoe crabs are often called ¿living fossils." However, they are not fossils. They are living.

Amino Acid Sequence↗
PubMed1996

The role of hemolymph coagulation in innate immunity.

Invertebrate animals, which lack adaptive immune systems, have developed defense systems that respond to common antigens on the surface of potential pathogens. Hemolymph coagulation is one such defense system in innate immunity. The discovery of lipopolysaccharide-sensitive and (1-->3)-beta-D-glucan-sensitive serine protease zymogens in horseshoe crab (limulus) hemocytes, both of which trigger the coagulation cascade, has exemplified how the animals detect and respond to foreign materials.

Amino Acid Sequence↗
PubMed1996

Crystal structure of H2-proteinase from the venom of Trimeresurus flavoviridis.

The crystal structure of the zinc-protease, H2-proteinase, isolated from the venom of Trimeresurus flavoviridis has been determined. The crystallographic R factor is 0.176 for 10,635 reflections with Fobs > 2sigma(Fobs) in the 8.0 to 2.2 Angstrom resolution range. The enzyme has two domains with a cleft in which a catalytic zinc atom is located. The N-terminal domain is composed of four helices around a central five-stranded beta-sheet. The irregularly folded C-terminal domain contains one helix and two disulfide bridges. These two domains are linked by a disulfide bridge. In the zinc environment, the catalytic zinc atom forms a distorted tetrahedral coordination with three histidines and one catalytic water molecule, and the methionine-containing turn is structurally conserved. These are distinctive features of the metzincins, one of the zinc metalloprotease superfamilies. The entire structure shows good agreement with that of two Crotalus snake venom proteases, adamalysin II and atrolysin C. The H2-proteinase, however, contains no structural calcium ions, and differences of disulfide configurations and the coordination of the catalytic water molecule exist as compared with the other two proteases.

Amino Acid Sequence↗
PubMed1996

A cysteine protease inhibitor stored in the large granules of horseshoe crab hemocytes: purification, characterization, cDNA cloning and tissue localization.

A cysteine protease inhibitor with an apparent Mr = 12,600, designated limulus (L)-cystatin, was isolated from hemocyte lysates of the Japanese horseshoe crab (Tachypleus tridentatus), using two steps of chromatography, including dextran sulfate-agarose, and carboxymethylated papain-agarose. L-cystatin inhibits amidolytic activity of papain by forming a noncovalent 1:1 complex with an equilibrium constant (Ki) of 0.08 nM. It also inhibits cathepsin L (Ki = 0.17 nM) and ficin (Ki = 0.52 nM), but not argingipain (a bacterial cysteine protease) and calpains. A cDNA for L-cystatin was isolated and the open reading frame coded for a mature protein of 114 amino acids, of which 99 residues were confirmed by peptide sequencing. L-cystatin shows significant sequence identities to members of the family 2 cystatin, such as bovine colostrum cystatin (33%) and human cystatin S (31%). Northern blotting revealed expression of the mRNA in hemocytes and slightly in heart but expression was negligible in hepatopancreas, intestine, stomach, and muscle. Immunoblotting revealed the localization to be in the large granules of hemocytes. Furthermore, L-cystatin has an antimicrobial activity against Gram-negative bacteria, which is much stronger than that of chicken egg white cystatin. These data suggest that the large granule-derived L-cystatin serves synergistically to accomplish an effective defense against invading microbes, together with other defense molecules that are released in response to external stimuli.

Agglutinins↗
PubMed1996

Tachycitin, a small granular component in horseshoe crab hemocytes, is an antimicrobial protein with chitin-binding activity.

Small granules of horseshoe crab hemocytes contain two known major antimicrobial substances, tachyplesin and big defensin (S5), and at least five protein components (S1 to S6), with unknown functions. In the present study, we examined the biological properties and primary structure of a small granular component S2, named tachycitin. This component was purified from the acid extract of hemocyte debris by two steps of chromatography. The purified tachycitin was a single chain protein with an apparent M(r) = 8,500 on Tricine-SDS-polyacrylamide gel electrophoresis. Ultracentrifugation analysis revealed tachycitin to be present in monomer form in solution. Tachycitin inhibited the growth of both Gram-negative and -positive bacteria, and fungi, with a bacterial agglutinating property. Moreover, tachycitin and big defensin acted synergistically in antimicrobial activities. The amino acid sequence and intrachain disulfide bonds of tachycitin were determined by amino acid and sequence analyses of peptides produced by enzymatic cleavages. The mature tachycitin consisted of 73 amino acid residues containing five disulfide bonds with no N-linked sugar. A cDNA coding for tachycitin was isolated from a hemocyte cDNA library. The open reading frame coded for an NH2-terminal signal sequence followed by the mature peptide and an extension sequence of -Gly-Arg-Lys at the COOH-terminus, which is a putative amidating signal. The COOH-terminal threonine amide released after digestion of tachycitin with lysylendopeptidase was identified. The NH2-terminal 28 residues of tachycitin shows sequence homology to a part of chitin-binding regions found in antifungal chitin-binding peptides, chitin-binding lectins, and chitinases, all of which have been isolated from plants. Tachycitin showed a specific binding to chitin but did not bind with the polysaccharides cellulose, mannan, xylan, and laminarin. Tachycitin may represent a new class of chitin-binding protein family in animals.

Amino Acid Sequence↗
PubMed1996

Molecular cloning of cDNA that encodes chymotrypsin inhibitor ECI from Erythrina variegata seeds and its expression in Escherichia coli.

Synthetic oligonucleotides representing all possible sequences of the N-terminal and internal amino acid sequences of the chymotrypsin inhibitor ECI from Erythrina variegata seeds were used to generate a probe specific for ECI-related sequences by the polymerase chain reaction on the E. variegata genomic DNA. A lambda phage cDNA library constructed from poly(A+) RNA from maturing seeds was screened with the ECI gene thus obtained as a probe and characterized by DNA sequencing. The cloned ECI cDNA comprised 737 nucleotides and one open reading frame that encoded a polypeptide chain of 203 amino acids including a signal peptide composed of 24 amino acids. An expression plasmid was designed for export of the recombinant inhibitor into the periplasm. For this purpose, the cDNA fragment encoding matured ECI was ligated into the NcoI and BamHI sites following the pel B signal sequence in the expression vector pET-22b and expressed in Escherichia coli BL21 (DE3). However, this attempt failed as the recombinant inhibitor caused the formation of inclusion bodies in E. coli cells as a heterologous preprotein (SR-ECI), with the pel B upstream leader. SR-ECI was made soluble and renatured by refolding and reoxidation, and subsequently processed with pronase to give rise to recombinant ECI (R-ECI) that had an extra methionine residue attached to the N-terminal amino acid of ECI. Purified R-ECI inhibited chymotrypsin almost as strongly as authentic ECI.

Amino Acid Sequence↗
PubMed1996

[Usefulness of the newly developed transtelephonic electrocardiogram and computer-supported response system].

The "Cardiophone System" is a system designed to expand the relationship between patients and medical services using a transtelephonic electrocardiogram and computer-assisted answering system. The transtelephonic electrocardiogram, or so-called "Cardiophone", developed by Nihon Kohden, Inc., allows the patients to carry a "Cardiophone" to record electrocardiograms during paroxysmal occurrences of palpitation, chest pain, and other symptoms. The Cardiophone may function as a terminal of the host computer at the hospital, which stores the electrocardiogram and print it as soon as the computer receives the electrocardiogram over the phone. Cardiologists can examine the electrocardiogram immediately after it is printed. Cardiologists and operators are on duty 24 hours a day. Judgments based on the electrocardiogram are made by the cardiologist on duty, and stored in the computer by the operator. The patients may listen to the judgment over the phone within 30 min of sending the electrocardiogram. In the case of potentially lethal findings on the electrocardiogram, the cardiologist on duty calls the patient directly to give a medical advice. We studied 184 outpatients who were enrolled in the Cardiophone System of our hospital. The average number of transtelephonic electrocardiograms was 10 per day. Abnormal electrocardiographic changes were observed in 42 patients, and the diagnoses were as follows: paroxysmal supraventricular tachycardia in 18 patients, paroxysmal atrial fibrillation in 17, ventricular tachycardia in 3, and angina in 7. Among seven patients in whom ST changes were documented by Cardiophone, six were diagnosed as variant angina. In several patients with diagnoses already made by Holter monitoring, the Cardiophone was used to monitor the drug effects and the correlations between symptoms and arrhythmic events. We conclude that the Cardiophone System is useful for diagnosing the causes of paroxysmal cardiac symptoms in some patients and for improving home medical services.

Adolescent↗
PubMed1995

Purification, characterization, and cDNA cloning of a 27-kDa lectin (L10) from horseshoe crab hemocytes.

We separated granular components of horseshoe crab hemocytes by a combination of centrifugation on sucrose density gradient and high performance liquid chromatography, and a 27-kDa protein termed L10 was found to be a major component in the large granules (Shigenaga, T., Takayenoki, Y., Kawasaki, S., Seki, N., Muta, T., Toh, Y., Ito, A., and Iwanaga, S. (1993) J. Biochem. (Tokyo) 114, 307-316). In the present work, lectin activity of this protein and its unique primary structure were elucidated. L10 was purified by four steps of chromatography, including dextran sulfate-Sepharose CL-6B, CM-Sepharose CL-6B, Sephacryl S-200, and Mono S. At least three 27-kDa isoproteins, named L10a, L10b, and L10c, were isolated. Their amino acid compositions were almost indistinguishable, and there were no amino sugars. All the isoforms had hemagglutinating activity against human A-type erythrocytes, in a Ca(2+)-independent manner with L10b showing the highest activity. The L10b-mediated hemagglutination was inhibited in the presence of N-acetylglucosamine or N-acetylallolactosamine, and the association constant (Ka) between L10b and N-acetylglucosamine was 1.95 x 10(4) M-1. Furthermore, L10b specifically agglutinated Staphylococcus saprophyticus KD. Ultracentrifugation analysis revealed that L10b is present in monomer form in solution. A cDNA coding for an isoform of L10 was isolated from a hemocyte cDNA library. The open reading frame of the 768-base pair cDNA coded for the signal sequence of 19 residues. The mature protein had 236 residues with the calculated molecular weight of 26,757. Amino acid sequences of the peptides derived from L10c exactly corresponded to the predicted sequence of the cDNA, whereas amino acid replacements of Ile-129 to Val and His-213 to Tyr existed both in L10a and L10b, suggesting that the cDNA codes for L10c. Cysteine was absent and there were five tandem repeats with 47 amino acids in each segment with internal sequence identities of 49-68%. The entire amino acid sequences had no significant sequence similarity with other known proteins.

Agglutination Tests↗
PubMed1995

Nucleotide sequence of the cDNA encoding the proenzyme of phenol oxidase A1 of Drosophila melanogaster.

Clones encoding pro-phenol oxidase [pro-PO; zymogen of phenol oxidase (monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1)] A1 were isolated from a lambda gt10 library that originated from Drosophila melanogaster strain Oregon-R male adults. The 2294 bp of the cDNA included a 13-bp 5'-noncoding region, a 2070-bp encoding open reading frame of 690 amino acids, and a 211-bp 3'-noncoding region. A hydrophobic NH2-terminal sequence for a signal peptide is absent in the protein. Furthermore, there are six potential N-glycosylation sites in the sequence, but no amino sugar was detected in the purified protein by amino acid analysis, indicating the lack of an N-linked sugar chain. The potential copper-binding sites, amino acids 200-248 and 359-414, are highly homologous to the corresponding sites of hemocyanin of the tarantula Eurypelma californicum, the horseshoe crab Limulus polyphemus, and the spiny lobster Panulirus interruptus. On the basis of the phylogenetic tree constructed by the neighbor-joining method, vertebrate tyrosinases and molluscan hemocyanins constitute one family, whereas pro-POs and arthropod hemocyanins group with another family. It seems, therefore, likely that pro-PO originates from a common ancestor with arthropod hemocyanins, independently to the vertebrate and microbial tyrosinases.

Amino Acid Sequence↗
PubMed1995

A novel type of limulus lectin-L6. Purification, primary structure, and antibacterial activity.

Lipopolysaccharide (LPS)-binding protein(s) was first screened in the detergent extract of horseshoe crab (limulus) hemocytes using LPS-immobilized agarose. A protein, designated L6 (M(r) = 27,000), was found to bind to LPS-agarose and was eluted with EDTA or o-phenanthroline. The L6 protein, however, did not inhibit the LPS-mediated activation of a limulus serine protease zymogen factor C. L6 had an affinity to the matrix of Sepharose CL-6B itself, and it could be eluted with high concentrations of monosaccharides (0.5-1.0 M), such as glucose, mannose, and galactose, suggesting a lectin-like nature. The entire amino acid sequence of L6 was determined by sequencing peptides derived from CNBr and enzymatic cleavages. L6 contained 7 half-cystines, and 1 cysteine residue at position 201 had a free SH-group. In addition, positions of the remaining three intrachain disulfide bonds were assigned by amino acid and sequence analyses of three cystinyl peptides produced by lysyl endopeptidase digestion. These results indicated that the entire sequence of L6 consisted of 221 residues with no N-linked sugar and was composed of six tandem repeats, each consisting of 33-38 amino acid residues. Inductively coupled plasma spectrometry of L6 indicated the presence of 0.75 mol zinc/mol of protein. No significant sequence homology was observed between L6 and other proteins, including various animal lectins and LPS-binding proteins. However, L6 showed agglutinating activity on LPS-coated sheep erythrocytes and Gram-negative and Gram-positive bacteria, it inhibited the growth of Gram-negative bacteria, and thus it presumably recognizes carbohydrate components in the cell wall of bacteria.

Amino Acid Sequence↗
PubMed1995

cDNA cloning and deduced amino acid sequence of prothrombin activator (ecarin) from Kenyan Echis carinatus venom.

The complete amino acid sequence of ecarin is deduced from the nucleotide sequence of a cDNA clone isolated by screening a venomous gland cDNA library of Kenyan Echis carinatus. The cDNA sequence with 2379 base pairs encodes an open reading frame of 616 amino acids with a remarkable sequence homology to the putative precursor protein of trigramin from Trimeresurus gramineus venom (61% identity) and a large hemorrhagin, jararhagin, from the pit viper Bothrops jararaca venom (62% identity). Thus, ecarin, as well as jararhagin and trigramin, is translated as a precursor protein, which may be processed posttranslationally. The ecarin proprotein has a "cysteine switch" motif (-Pro-Lys-Met-Cys-Gly-Val-) similar to that involved in the activation of matrix metalloproteinase zymogens. The processed mature protein consists of 426 amino acid residues (residues 191-616), showing the strongest sequence similarity with that of Russell's viper venom factor X activator (RVV-X) heavy chain (64% identity). Like RVV-X heavy chain, ecarin contains metalloproteinase, disintegrin, and cysteine-rich domains. The metalloproteinase domain has a typical zinc-chelating sequence (-His-Glu-Xaa-Xaa-His-Xaa-Xaa-Gly-Xaa-Xaa-His-), as found in crayfish astacin. In the disintegrin domain of ecarin, the Arg-Gly-Asp sequence is replaced by Arg-Asp-Asp, as found in the disintegrin domains of RVV-X heavy chain (Arg-Asp-Glu) and a guinea pig sperm fusion protein, PH-30 beta (Thr-Asp-Glu). These findings show that while there are structural and evolutionary relationships among these proteins, each has a unique functional activity.

Amino Acid Sequence↗
PubMed1995

A limulus intracellular coagulation inhibitor type 2. Purification, characterization, cDNA cloning, and tissue localization.

We described in a foregoing report findings on serpin, a serine protease inhibitor, newly identified in horseshoe crab (Tachypleus tridentatus) hemocytes and we name it limulus intracellular coagulation inhibitor, LICI (Miura, Y., Kawabata, S., and Iwanaga, S. (1994) J. Biol. Chem. 269, 542-547). This serpin specifically inhibits limulus lipopolysaccharide-sensitive serine protease, factor C. In ongoing studies on limulus serpin, we have found another inhibitor, LICI type-2 (LICI-2), which inhibits not only factor C (k1 = 7.1 x 10(4) M-1 S-1) but also limulus clotting enzyme (k1 = 4.3 x 10(5) M-1 S-1). LICI-2 inhibits mammalian serine proteases, including alpha-thrombin, salivary kallikrein, plasmin, and tissue plasminogen activator. The inactivation of plasmin is the most rapid (k1 = 1.2 x 10(6) M-1 S-1). The purified LICI-2 is a single chain glycoprotein with an apparent M(r) = 42,000. A cDNA for LICI-2 was isolated and the open reading frame coded for a mature protein of 386 amino acids, of which 160 residues were confirmed by peptide sequencing. Although LICI-2 shows significant sequence similarity to the previous limulus serpin, LICI-1 (42% identity), LICI-2 contains a unique putative reactive site, -Lys-Ser-, distinct from that of LICI-1 (-Arg-Ser-). Northern blotting revealed expression of LICI-2 mRNA only in hemocytes, and not in heart, brain, stomach, intestine, coxal gland, and skeletal muscle. The immunoblot of large and small granule components with antiserum against purified LICI-2 suggests that LICI-2 is stored specifically in large granules, as in the case of LICI-1, and is released in response to external stimuli. We propose that the LICIs be classified into a new subfamily of intracellular serpins, regulated secretory serpins.

Amino Acid Sequence↗
PubMed1995

Purified horseshoe crab factor G. Reconstitution and characterization of the (1-->3)-beta-D-glucan-sensitive serine protease cascade.

Horseshoe crab hemocyte lysate responds to (1-->3)-beta-D-glucans, initiating an enzymatic cascade, which culuminates in clot formation. We have purified to homogeneity the serine protease zymogen factor G, which is directly activated by (1-->3)-beta-D-glucans and which initiates the hemolymph clotting cascade. Factor G is a heterodimeric protein composed of two noncovalently associated subunits alpha (72 kDa) and beta (37 kDa). In the presence of (1-->3)-beta-D-glucans such as curdlan and paramylon, factor G is autocatalytically activated to an active serine protease named factor G. This activation is accompanied by limited proteolysis of both subunits: the 72-kDa subunit alpha is cleaved to 55-kDa and 17-kDa fragments, and the 37-kDa subunit beta is shortened to 34 kDa. Longer incubations with (1-->3)-beta-D-glucans result in cleavage of the 55-kDa fragment to 46 kDa and the 34-kDa fragment to 32 kDa, with concomitant loss of amidase activity. Reconstitution experiments using purified proteins participating in the hemolymph clotting cascade demonstrate that factor G is capable of activating proclotting enzyme directly, resulting in the conversion of coagulogen to coagulin gel. Thus, purified factor G is shown to be the primary initiator of the (1-->3)-beta-D-glucan-sensitive coagulation pathway in the horseshoe crab hemocyte lysate.

Amino Acid Sequence↗
PubMed1995

A novel big defensin identified in horseshoe crab hemocytes: isolation, amino acid sequence, and antibacterial activity.

Hemocytes of the horseshoe crab (limulus) contain a family of arthropodous peptide antibiotics, termed the tachyplesin family, and antibacterial protein, called anti-LPS factor, of which the former is located in the small (S) granules and the latter in the large (L) granules of the hemocytes. In our ongoing studies on granular components, we have identified here a novel defensin-like substance present in both L- and S-granules. This substance strongly inhibits the growth of Gram-negative and -positive bacteria, and fungi, such as Candida albicans. The isolated substance, tentatively termed "big defensin," consists of 79 amino acid residues, of which the COOH-terminal 37 residues have a sequence similar to those of mammalian neutrophil-derived defensins, especially rat defensin. Characterization of the disulfide motif in big defensin indicated that the disulfide array is identical to that of beta-defensins from bovine neutrophils. One clear structural difference is that the limulus hemocyte-derived big defensin has an extension of the NH2-terminal hydrophobic sequence with 35 amino acid residues followed by the COOH-terminal cationic defensin portion. This amphipathic nature of big defensin seems likely to be associated with its potent antibacterial activity. Furthermore, antibacterial activities of the NH2-terminal hydrophobic region and the COOH-terminal defensin portion separated by tryptic digestion are significantly different: the former displays a more potent activity against Gram-positive bacteria, whereas the latter is more potent against Gram-negative bacteria. Big defensin, therefore, may prove to represent a new class of defensin family possessing two functional domains with different antimicrobial activities.

Amino Acid Sequence↗
PubMed1995

Crystallization and preliminary X-ray study of H2-proteinase from the venom of Trimeresurus flavoviridis.

H2-proteinase, a non-hemorrhagic metalloproteinase from the venom of Trimeresurus flavoviridis, has been crystallized by vapor diffusion from solutions containing ammonium sulfate. The crystals belong to the tetragonal space group, P41212 or P43212, with unit cell dimensions of a = b = 77.8 A and c = 82.3 A. The asymmetric unit contains one protein molecule. Diffraction data for a native crystal were collected up to 2.0 A resolution.

Animals↗
PubMed1995

Substrate specificity of rabbit liver metalloendopeptidase and its new fluorogenic peptide substrates.

A metalloendopeptidase (MEP) isolated from rabbit liver microsomes with substrate specificity for peptides containing Arg at the P1 and P4 positions has recently proved to be identical to soluble angiotensin-binding protein present in the cytosol. Here we describe the peptide-degrading specificity of MEP, determined using various bioactive peptides and novel fluorogenic substrates for the enzyme. MEP degraded oligopeptides, including bradykinin, alpha-neoendorphin, bovine adrenal medulla dodecapeptide, substance P, bombesin, neurotensin, and alpha-endorphin, but not polypeptides such as reduced lysozyme and histone H4, hence, MEP probably belongs to the family of endo-oligopeptidases. It cleaved most preferentially at the -Phe-Ser- bond of bradykinin (kcat/Km = 2.8 x 10(4) M-1.S-1) but did not cleave high molecular weight and low molecular weight kininogens, the precursors of bradykinin. MEP did not cleave angiotensin I, dynorphin A 1-13, somatostatin, and luteinizing hormone-releasing hormone, some of which are good substrates for metalloendopeptidase-24.15, metalloendopeptidase-24.16, N-arginine dibasic convertase, and yeast endopeptidase-24.15 related peptidase. An active site-directed inhibitor of metalloendopeptidase-24.15, N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate also had no effects on the amidolytic activity of MEP. Based on the cleavage sites of bioactive peptides and processing sites of vitamin K-dependent proproteins, intramolecularly quenched fluorogenic peptide substrates were newly synthesized. Among the thirteen substrates used, the most reactive was 2-aminobenzoyl-Ala-Arg-Val-Arg-Arg-Ala- Asn-Ser-2,4-dinitroanilinoethylamide (kcat/Km = 9.3 x 10(5) M-1.S-1). An angiotensin antagonist, [Sar1, Ala8]-angiotensin II, inhibited hydrolysis of the substrate by MEP in a competitive manner (Kl = 7.6 microM). MEP cleaved oligopeptides even on the carboxyl side of proline residue and these peptides are resistant to hydrolysis by the cytosol-derived proteasome, therefore MEP may participate in the catabolism of oligopeptides in the cytosol, together with other endo-oligopeptidases.

Amino Acid Sequence↗