Ebook: Aspartic Proteinases: Structure, Function, Biology, and Biomedical Implications

The 5th International Conference on Aspartic Proteinases was held on September 19 through 24, 1993, at Naito Museum of Pharmaceutical Science and Industry, Kawashima­ cho, Gifu Prefecture, Japan, about 15 miles northwest of Nagoya City. About 100 scientists attended the conference, including 52 from 14 countries outside Japan, and 32 papers were presented by invited speakers, and 58 papers as posters. The purpose of this conference was to present and discuss new information on the structure, function, and biology, and related topics, including biomedical implications, of aspartic proteinases, and this book is a collec­ tion of nearly all the papers presented at the meeting. Aspartic proteinases belong to one of the four major classes of proteinases, the others being serine, cysteine, and metalloproteinases, and are so called since they have two catalytic aspartic acid residues in common in their active sites. Most of them are optimally active at acidic pH, hence the long-used name "acid proteinases," which, indeed, was the major title of the first conference of this series. However, some of them are active at around neutral pH, indicating their physiological roles in a wider range of pH than hitherto considered.

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Content:
Front Matter....Pages i-xxvi
Comparison of the Active Site Specificity of the Aspartic Proteinases Based on a Systematic Series of Peptide Substrates....Pages 1-9
The Molecular Structure of Human Progastricsin and its Comparison with that of Porcine Pepsinogen....Pages 11-18
A New Way of Looking at Aspartic Proteinase Structures: A Comparison of Pepsin Structure to other Aspartic Proteinases in the Near Active Site Region....Pages 19-32
Rearranging Pepsinogen and Pepsin by Protein Engineering....Pages 33-40
Comparative Investigations on Pig Gastric Proteases and Their Zymogens....Pages 41-51
Non-Mammalian Vertebrate Pepsinogens and Pepsins: Isolation and Characterization....Pages 53-65
Transcription Regulation of Human and Porcine Pepsinogen A....Pages 67-75
A Comparative Study on Amino Acid Sequences of Three Major Isoforms of Human Pepsin A....Pages 77-81
Molecular Mass Determination by Electrospray Mass Spectrometry of Human Pepsins, Gastricsin, and Porcine Pepsin A Variants....Pages 83-89
Evidence for Electrostatic Interactions in the S2 Subsite of Porcine Pepsin....Pages 91-94
Protein Engineering of Surface Loops: Preliminary X-Ray Analysis of the Chy155–165rhi Mutant....Pages 95-99
Seminal Progastricsin....Pages 101-105
Effects of Hydrocortisone on the Pepsinogen-Producing Cells in Rat Stomach Mucosa....Pages 107-113
Effects of Omeprazole, a Proton Pump Inhibitor, on Pepsinogen-Producing Cells, with Special Reference to Neonatal Development....Pages 115-123
Transcription of Embryonic Chick Pepsinogen Gene is Affected by Mesenchymal Signals through its 5?-Flanking Region....Pages 125-129
Serum Pepsinogen Values as Possible Markers for Evaluating the Possibility of Peptic Ulcer Recurrence under H2-Blocker Half-Dose Maintenance Therapy....Pages 131-137
The Clinical Application of the Serum Pepsinogen I And II Levels as a Mass Screening Method for Gastric Cancer....Pages 139-143
A Minute Gastric Cancer Detected by a New Screening Method Using Serum Pepsinogen I and II....Pages 145-148
Two Cases of Early Colorectal Cancer Associated with Gastric Adenoma Detected by Serum Pepsinogen Screening Method....Pages 149-154
Comparisons of the Three-Dimensional Structures, Specificities and Glycosylation of Renins, Yeast Proteinase A and Cathepsin D....Pages 155-166
Discovery of Inhibitors of Human Renin with High Oral Bioavailability....Pages 167-180
Structure of Human Cathepsin D: Comparison of Inhibitor Binding and Subdomain Displacement with other Aspartic Proteases....Pages 181-192
Cathepsin D Crystal Structures and Lysosomal Sorting....Pages 193-200
Isolation and Characterization of Human Gastric Procathepsin E and Cathepsin E....Pages 201-210
Isolation, Characterization, and Structure of Procathepsin E and Cathepsin E from the Gastric Mucosa of Guinea Pig....Pages 211-221
Cathepsin E and Cathepsin D: Biosynthesis, Processing and Subcellular Location....Pages 223-229
Glycoproteins of the Aspartyl Proteinase Gene Family Secreted by the Developing Placenta....Pages 231-240
Structure and Possible Function of Aspartic Proteinases in Barley and other Plants....Pages 241-254
Aspartic Proteinases (Cyprosins) from Cynara Cardunculus Spp. Flavescens Cv. Cardoon; Purification, Characterisation, and Tissue-Specific Expression....Pages 255-266
Acid-Activation of Rat Prorenin following Non-Proteolytic Alteration....Pages 267-272
Human Procathepsin D: Three-Dimensional Model and Isolation....Pages 273-278
Identification of Five Molecular forms of Cathepsin D in Bovine Milk....Pages 279-283
Site-Directed Mutagenesis of a Disulfide Bridge in Cathepsin D: Expression, Activation, Purification, and Characterization....Pages 285-287
Expression of Rat Cathepsin D cDNA in Saccharomyces Cerevisiae: Intracellular Sorting of Cathepsin D to Yeast Vacuole....Pages 289-292
Molecular Cloning and Immunocytochemical Localization of Jasmonic Acid Inducible Cathepsin D Inhibitors from Potato....Pages 293-298
Purification and Characterization of an Acid Proteinase from Dirofilaria Immitis Worms....Pages 299-304
Inhibition and Entrapment of Aspartic Proteinases by ?2-Macroglobulin....Pages 305-313
Recombinant Human Cathepsin E....Pages 315-318
Purification and Characterization of Recombinant Human Cathepsin E....Pages 319-324
Comparison of Biochemical Properties of Natural and Recombinant Cathepsin E....Pages 325-330
Increased Expression and Specific Localization of Cathepsins E and D in Vulnerable Brain Regions of Aged and Postischemic Rats....Pages 331-334
Characterization of Cathepsins E and D Accumulated at Early Stages of Neuronal Damage in Hippocampal Neurons of Rats....Pages 335-339
Functional Aspects of Cathepsin E: Is it an Embryonic or Fetal Type of Aspartic Proteinase?....Pages 341-343
Tissue- and Cell-Specific Control of Guinea Pig Cathepsin E Gene Expression....Pages 345-348
Cathepsin E is Expressed in Fetal Rat Glandular Stomach Epithelial Cells in Primary Culture in the Absence of Mesenchymes....Pages 349-355
Cathepsin E Expressed in Pancreatic Cancer....Pages 357-361
Plant Aspartic Proteinases from Cynara Cardunculus Spp. Flavescens Cv. Cardoon; Nucleotide Sequence of a cDNA Encoding Cyprosin and its Organ-Specific Expression....Pages 363-366
Cardosin A and B, Aspartic Proteases from the Flowers of Cardoon....Pages 367-372
Mechanism of Autoprocessing of a Mini-Precursor of the Aspartic Protease of Human Immunodeficiency Virus Type 1....Pages 373-377
Mutants of HIV-1 Protease with Enhanced Stability to Autodegradation....Pages 379-386
Identification of Amino Acid Residues of the Retroviral Aspartic Proteinases Important for Substrate Specificity and Catalytic Efficiency....Pages 387-398
Inhibitor-Resistant Mutants of the HIV-1 Aspartic Protease....Pages 399-406
Design and Synthesis of HIV Protease Inhibitors Containing Allophenylnorstatine as a Transition-State Mimic....Pages 407-411
Breaking the Shackles of the Genetic Code: Engineering Retroviral Proteases Through Total Chemical Synthesis....Pages 413-423
X-Ray Structure of a Tethered Dimer for HIV-1 Protease....Pages 425-438
Structure of HIV-1 Protease with KNI-272: A Transition State mimetic Inhibitor Containing Allophenylnorstatine....Pages 439-444
Molecular Dynamics of HIV-1 Protease in Complex with a Difluoroketone-Containing Inhibitor: Implications for the Catalytic Mechanism....Pages 445-449
Activated Dynamics of Flap Opening in Hiv-1 Protease....Pages 451-454
Computer Simulation and Analysis of the Reaction Pathway for the Decomposition of the Hydrated Peptide Bond in Aspartic Proteases....Pages 455-460
Activities of Precursor and Tethered Dimer Forms of HIV Proteinase....Pages 461-465
Site-Directed Mutagenesis of HIV-1 Protease: Generation of Mutant Proteases with Increased Stability to Autodigestion....Pages 467-472
Molecular Modeling of the Structure of FIV Protease....Pages 473-477
Extracellular Aspartic Proteinases from Candida Yeasts....Pages 479-484
Tyrosine 75 on the Flap Contributes to Enhance Catalytic Efficiency of a Fungal Aspartic Proteinase, Mucor Pusillus Pepsin....Pages 485-488
Yeast and Mammalian Basic Residue-Specific Aspartic Proteases in Prohormone Conversion....Pages 489-500
Pepstatin-Insensitive Carboxyl Proteinases....Pages 501-509
The Three-Dimensional X-Ray Crystal Structure of the Aspartic Proteinase Native to Trichoderma Reesei Complexed with a Renin Inhibitor CP-80794....Pages 511-518
A Quantum Mechanical Model of the Hydration and Acidity of the Active Site in Aspartic Proteases....Pages 519-527
Site-Directed Mutagenesis of Rhizopuspepsin: An Analysis of Unique Specificity....Pages 529-542
Site-Directed Mutagenesis Revealed Role of Subsite Residues of Mucor Pusillus Pepsin in Catalytic Function....Pages 543-547
Expression in E.Coli of Aspergillus Niger Var. Macrosporus Proteinase A, a Non-Pepsin Type Acid Proteinase....Pages 549-554
X-Ray Crystallographic Study of a Non-Pepsin-Type Acid Proteinase, Aspergillus Niger Proteinase A....Pages 555-558
Conformation Analysis of Non-Pepsin-Type Acid Proteinase a from the Fungus Aspergillus Niger by NMR....Pages 559-563
Back Matter....Pages 565-568
....Pages 569-572