The Experts below are selected from a list of 165 Experts worldwide ranked by ideXlab platform
Nancy A. Thornberry - One of the best experts on this subject based on the ideXlab platform.
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Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII
2015Co-Authors: Jonathan A. Ellman, Richard T. Cummings, Nancy A. ThornberryAbstract:There is currently intense interest in the emerging group of proline-specific Dipeptidases, and their roles in the regulation of biological processes. Dipeptidyl peptidase IV (DPP-IV) is involved in glucose metabolism by contributing to the regulation of glucagon family peptides and has emerged as a potential target for the treatment of metabolic diseases. Two other proline-specific Dipeptidases, DPP-VII (also known as quiescent cell proline dipeptidase) and DPP-II, have unknown functions and have recently been suggested to be identical proteases based on a sequence comparison of human DPP-VII and rat DPP-II (78
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Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII
Biochemical Journal, 2003Co-Authors: Barbara Leiting, Jonathan A. Ellman, Richard T. Cummings, Kellyann D. Pryor, Joseph K. Wu, Frank Marsilio, Reshma A. Patel, Charles S. Craik, Nancy A. ThornberryAbstract:There is currently intense interest in the emerging group of proline-specific Dipeptidases, and their roles in the regulation of biological processes. Dipeptidyl peptidase IV (DPP-IV) is involved in glucose metabolism by contributing to the regulation of glucagon family peptides and has emerged as a potential target for the treatment of metabolic diseases. Two other prolinespecific Dipeptidases, DPP-VII (also known as quiescent cell proline dipeptidase) and DPP-II, have unknown functions and have recently been suggested to be identical proteases based on a sequence comparison of human DPP-VII and rat DPP-II (78% identity) [Araki, Li, Yamamoto, Haneda, Nishi, Kikkawa and Ohkubo (2001) J. Biochem. 129, 279‐288; Fukasawa, Fukasawa, Higaki, Shiina, Ohno, Ito, Otogoto and Ota (2001) Biochem. J. 353, 283‐290]. To facilitate the identification of selective sub
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Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII.
The Biochemical journal, 2003Co-Authors: Barbara Leiting, Jonathan A. Ellman, Richard T. Cummings, Kellyann D. Pryor, Joseph K. Wu, Frank Marsilio, Reshma A. Patel, Charles S. Craik, Nancy A. ThornberryAbstract:There is currently intense interest in the emerging group of proline-specific Dipeptidases, and their roles in the regulation of biological processes. Dipeptidyl peptidase IV (DPP-IV) is involved in glucose metabolism by contributing to the regulation of glucagon family peptides and has emerged as a potential target for the treatment of metabolic diseases. Two other proline-specific Dipeptidases, DPP-VII (also known as quiescent cell proline dipeptidase) and DPP-II, have unknown functions and have recently been suggested to be identical proteases based on a sequence comparison of human DPP-VII and rat DPP-II (78% identity) [Araki, Li, Yamamoto, Haneda, Nishi, Kikkawa and Ohkubo (2001) J. Biochem. 129, 279-288; Fukasawa, Fukasawa, Higaki, Shiina, Ohno, Ito, Otogoto and Ota (2001) Biochem. J. 353, 283-290]. To facilitate the identification of selective substrates and inhibitors for these enzymes, a complete biochemical profile of these enzymes was obtained. The pH profiles, substrate specificities as determined by positional scanning, Michaelis-Menten constants and inhibition profiles for DPP-VII and DPP-II were shown to be virtually identical, strongly supporting the hypothesis that they are the same protease. In addition, substrate specificities, catalytic constants and IC(50) values were shown to be markedly different from those of DPP-IV. Selective DPP-IV and DPP-VII substrates were identified and they can be used to design selective inhibitors and probe further into the biology of these enzymes.
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Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII - eScholarship
2003Co-Authors: Barbara Leiting, Jonathan A. Ellman, Richard T. Cummings, Kellyann D. Pryor, Joseph K. Wu, Frank Marsilio, Reshma A. Patel, Charles S. Craik, Nancy A. ThornberryAbstract:There is currently intense interest in the emerging group of proline-specific Dipeptidases, and their roles in the regulation of biological processes. Dipeptidyl peptidase IV (DPP-IV) is involved in glucose metabolism by contributing to the regulation of glucagon family peptides and has emerged as a potential target for the treatment of metabolic diseases. Two other proline-specific Dipeptidases, DPP-VII (also known as quiescent cell proline dipeptidase) and DPP-II, have unknown functions and have recently been suggested to be identical proteases based on a sequence comparison of human DPP-VII and rat DPP-II (78% identity) [Araki, Li, Yamamoto, Haneda, Nishi, Kikkawa and Ohkubo (2001) J. Biochem. 129,279-288; Fukasawa, Fukasawa, Higaki, Shiina, Ohno, Ito, Otogoto and Ota (2001) Biochem. J. 353, 283-290]. To facilitate the identification of selective substrates and inhibitors for these enzymes, a complete biochemical profile of these enzymes was obtained. The pH profiles, substrate specificities as determined by positional scanning, Michaelis-Menten constants and inhibition profiles for DPP-VII and DPP-II were shown to be virtually identical, strongly supporting the hypothesis that they are the same protease. In addition, substrate specificities, catalytic constants and IC50 values were shown to be markedly different from those of DPP-IV. Selective DPP-IV and DPP-VII substrates were identified and they can be used to design selective inhibitors and probe further into the biology of these enzymes.
Lars Josefsson - One of the best experts on this subject based on the ideXlab platform.
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Histological Localization of Two Dipeptidases in the Pig Small Intestine and Liver, Using Immunofluorescence
Gastroenterology, 2020Co-Authors: Ove Norén, Hans Sjöström, Erik Dabelsteen, Lars JosefssonAbstract:Antibodies were raised in rabbits against glycylleucine dipeptidase (EC 3.4.13.2) and proline dipeptidase (EC 3.4.13.9) purified from the pig. IgG fractions were isolated and purified by affinity chromatography on Sepharose (dipeptidase) columns and then used in histological studies on the small intestine and the liver from pig, using the double layer immunofluorescence-staining technique. In the small intestine the Dipeptidases were predominantly localized in the cytoplasm of the enterocytes. A reaction was also seen in the leukocyte cytoplasm in the stroma of the small intestine. The Dipeptidases were present in the villi but not in the crypts. In the liver the Dipeptidases were localized, in the cytoplasm of the hepatocyte, but strong fluorescence was also obtained in the epithelium of the bile ducts. Glycylleucine dipeptidase and proline dipeptidase have been isolated from liver tissue and they were shown to be immunologically identical with the purified intestinal Dipeptidases.
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Ciba Foundation Symposium 50 - Peptide Transport and Hydrolysis - Intracellular hydrolysis of peptides.
Ciba Foundation symposium, 2008Co-Authors: Lars Josefsson, Hans Sjöström, Ove NorénAbstract:Purification of the first Dipeptidases, glycylleucine dipeptidase (EC 3.4.13.2) and proline dipeptidase (EC 3.4.13.9), from intestine, have shown them to be true Dipeptidases, hydrolysing only dipeptides in their laevo form. Although they have quite different specificities they show great similarities in their chemical and physicochemical properties. Specific antibodies against the two Dipeptidases have been raised and used in combination with the double-layer immunofluorescent staining technique to study their histological localization in the small intestine. The results conclusively demonstrated that both glycylleucine dipeptidase and proline dipeptidase are exclusively located in the cytosol of the enterocytes. This location fits well with the current idea of transport and hydrolysis of dipeptides in the intestine where the dipeptides are taken by a specific transport mechanism and are hydrolysed intracellularly. Although it is tempting to add a specific role for the Dipeptidases of the enterocytes in the final digestion of exogenous proteins, studies so far have shown their identity with the corresponding Dipeptidases of other tissues. It is therefore suggested that their role in the digestion process may be based entirely on their abundance in the intestine.
Haeng Soon Park - One of the best experts on this subject based on the ideXlab platform.
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Glycosyl-phosphatidylinositol (GPI)-anchored renal dipeptidase is released by a phospholipase C in vivo.
Kidney & blood pressure research, 2002Co-Authors: Sung Wook Park, Nigel M. Hooper, Anthony J. Turner, Hwanghee Blaise Lee, Kyong Choi, Sung Kwang Park, Haeng Soon ParkAbstract:The release mechanism of the glycosyl-phosphatidylinositol (GPI)-anchored renal dipeptidase (EC 3.4.13.19) in vivo has been investigated. Triton X-114 phase separation indicated that the dipeptidase is exclusively present as a hydrophilic form in urine from porcine, rat, rabbit and human. Western blot analysis of human and porcine purified dipeptidase and the urine concentrates with anti-(cross-reacting determinant) serum demonstrated the presence of inositol 1,2-cyclic monophosphate indicating that the renal dipeptidase had been released from the membrane by the action of a phospholipase C. This is the first direct evidence for cleavage of a human GPI-anchored protein by a responsible phospholipase C in vivo.
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IDENTIFICATION OF URINARY DIPEPTIDASE AS THE RELEASED FORM OF RENAL DIPEPTIDASE
Kidney & blood pressure research, 1997Co-Authors: Bok Yun Kang, Jae Cheon Lee, Hwanghee Blaise Lee, Haeng Soon ParkAbstract:Amphipathic and hydrophilic forms of human renal dipeptidase and urinary dipeptidase were purified by affinity chromatography using cilastatin, a dipeptidase inhibitor, as the ligand. The sequence analyses of the first ten amino acids of renal and urinary Dipeptidases were shown to be identical, and they are Asp-Phe-Phe-Arg-Asp-Glu-Ala-Glu-Arg-Ile. Unambiguous results of amino acid sequencing, the molecular weight of native protein (190 kD), the molecular weight of subunit (47.7 kD) and a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicate that the enzymes are composed of homotetramers. This is the most direct evidence that urinary dipeptidase is the released form of renal dipeptidase. In fact, they are the same enzymes.
Masanobu Kohsaka - One of the best experts on this subject based on the ideXlab platform.
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Gene Structural Analysis and Expression of Human Renal Dipeptidase
Biotechnology progress, 1994Co-Authors: Susumu Satoh, Chihiro Kusunoki, Yoshiyuki Konta, Mineo Niwa, Kazuyuki Ohtsuka, Yuriko Keida, Masanobu KohsakaAbstract:Human renal dipeptidase cDNA and genomic DNA were isolated from human kidney cDNA and genomic libraries, respectively. The human renal dipeptidase gene has a total length of approximately 6 kb and consists of ten exons and nine introns. The exons and cDNA each encode the 411 amino acid residues of the precursor protein, including 16 amino acid residues of signal sequence and a hydrophobic carboxyl terminal sequence for the attachment of a phosphatidylinositol glycan. Although the cDNA was slightly different from the cDNA reported by Adachi et al. (1990), the differences observed suggest, by comparison with human genomic DNA, that it may not represent an allelic variant but a cloning artifact. The recombinant human renal dipeptidase was produced on the surface of transfected L929 cells and had the same character as native renal dipeptidase. Northern blotting hybridization analysis showed that renal dipeptidase mRNA is only transcribed in kidney.
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Cloning and structural analysis of genomic DNA for human renal dipeptidase.
Biochimica et biophysica acta, 1993Co-Authors: Susumu Satoh, Chihiro Kusunoki, Yoshiyuki Konta, Mineo Niwa, Masanobu KohsakaAbstract:A genomic DNA for human renal dipeptidase was isolated from a human genomic library using probes for human renal dipeptidase cDNA. The human renal dipeptidase gene, containing ten exons and nine introns, had a total length of approx. 6 kbp. The DNA sequence of these exons was slightly different from that of the human renal dipeptidase cDNA reported by Adachi et al. [1]. From the results of a comparison of the deduced amino acid sequence of each exon with various mammalian renal Dipeptidases, the fourth exon was found to be highly conserved (90%).
Ove Norén - One of the best experts on this subject based on the ideXlab platform.
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Histological Localization of Two Dipeptidases in the Pig Small Intestine and Liver, Using Immunofluorescence
Gastroenterology, 2020Co-Authors: Ove Norén, Hans Sjöström, Erik Dabelsteen, Lars JosefssonAbstract:Antibodies were raised in rabbits against glycylleucine dipeptidase (EC 3.4.13.2) and proline dipeptidase (EC 3.4.13.9) purified from the pig. IgG fractions were isolated and purified by affinity chromatography on Sepharose (dipeptidase) columns and then used in histological studies on the small intestine and the liver from pig, using the double layer immunofluorescence-staining technique. In the small intestine the Dipeptidases were predominantly localized in the cytoplasm of the enterocytes. A reaction was also seen in the leukocyte cytoplasm in the stroma of the small intestine. The Dipeptidases were present in the villi but not in the crypts. In the liver the Dipeptidases were localized, in the cytoplasm of the hepatocyte, but strong fluorescence was also obtained in the epithelium of the bile ducts. Glycylleucine dipeptidase and proline dipeptidase have been isolated from liver tissue and they were shown to be immunologically identical with the purified intestinal Dipeptidases.
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Size and shape of two intestinal Dipeptidases.
International journal of peptide and protein research, 2009Co-Authors: Hans Sjöström, Ove NorénAbstract:Physicochemical parameters were determined on glycyl-L-leucine hydrolase (glycyl-leucine dipeptidase, EC 3.4.13.2) and aminoacyl-L-proline hydrolase (proline dipeptidase, EC 3.4.13.9), purified from pig small intestine. The native molecular weights were found to be 115,000 and 113,000, respectively, as determined by a sedimentation equilibrium technique. Under denaturing conditions the molecular weights were found to be 51,000 and 63,200, respectivemy, using the same technique. It is concluded that each dipeptidase is composed of two subunits of equal molecular weight. The two Dipeptidases have the same Stokes radius, 4.2 nm, analysed by gel chromatography. The sedimentation coefficients were found to be 5.8 S and 6.5 S and the intrinsic viscosities 5.4 ml/g and 5.8 ml/g, respectively. For both Dipeptidases the measured physicochemical parameters are in accordance with the model of a prolate ellipsoid of revolution, having an axial ratio of about 5.
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Ciba Foundation Symposium 50 - Peptide Transport and Hydrolysis - Intracellular hydrolysis of peptides.
Ciba Foundation symposium, 2008Co-Authors: Lars Josefsson, Hans Sjöström, Ove NorénAbstract:Purification of the first Dipeptidases, glycylleucine dipeptidase (EC 3.4.13.2) and proline dipeptidase (EC 3.4.13.9), from intestine, have shown them to be true Dipeptidases, hydrolysing only dipeptides in their laevo form. Although they have quite different specificities they show great similarities in their chemical and physicochemical properties. Specific antibodies against the two Dipeptidases have been raised and used in combination with the double-layer immunofluorescent staining technique to study their histological localization in the small intestine. The results conclusively demonstrated that both glycylleucine dipeptidase and proline dipeptidase are exclusively located in the cytosol of the enterocytes. This location fits well with the current idea of transport and hydrolysis of dipeptides in the intestine where the dipeptides are taken by a specific transport mechanism and are hydrolysed intracellularly. Although it is tempting to add a specific role for the Dipeptidases of the enterocytes in the final digestion of exogenous proteins, studies so far have shown their identity with the corresponding Dipeptidases of other tissues. It is therefore suggested that their role in the digestion process may be based entirely on their abundance in the intestine.