Enzymes (eBook)

Protein Methyltransferases

Steven G. Clarke, Fuyuhiko Tamanoi (Herausgeber)

eBook Download: PDF

2011 | 1. Auflage
592 Seiten
Elsevier Science (Verlag)
978-0-08-046042-0 (ISBN)

Infos

Protein methylation has recently emerged as one of the most exciting areas of study on posttranslational modification. A large family of protein methyltransferases has been identified and their structural properties have been characterized. These studies have provided novel insights into how methylation regulates a variety of biological functions including DNA and RNA metabolism, protein synthesis and signal transduction. Methylation also plays important roles in aging. This volume is intended to capture these recent developments concerning protein methyltransferases.

Inhalt

Cover 1
Contents 5
Preface 11
Overview of Protein Methyltransferases 13
Protein Methyltransferases:Their Distribution Among the Five Structural Classes of AdoMet-Dependent Methyltransferases1 15
I. Abstract 16
II. Introduction 16
III. Class I MTases: In the Beginning, an MTase Was an MTase Was an MTase 18
IV. Class II MTases: A Lesson in Cobalamin 21
V. Class III MTases: Another Lesson in Cobalamin 21
VI. Class IV MTases: Knotty New Structure SPOUTs 24
VII. Class V MTases: Pseudo Knotty Structures Come in SETs 26
VIII. Conformations of AdoMet and AdoHcy 28
IX. Diverse Set of Mechanisms for a Conserved Class of MTase 30
X. Conclusions 33
Modification of Lysine and Arginine Residues in Signal Transduction, Transcription, Translation, and Other Functions 41
The Family of Protein Arginine Methyltransferases* 43
I. Abstract 43
II. Introduction 44
III. The Protein Arginine Methyltransferases Family of Enzymes 45
IV. Mammalian Protein Arginine Methyltransferases 47
V. Yeast Protein Arginine Methyltransferases 53
VI. PRMT Substrate Specificity 55
VII. Small-Molecule Inhibitors of Protein Arginine Methyltransferases 55
Diverse Roles of Protein Arginine Methyltransferases 63
I. Abstract 63
II. Introduction 64
III. Arginine Methylation and Intermolecular Interactions 71
IV. Roles of PRMTs in Cellular Processes 73
V. Roles of Protein Arginine Methyltransferases in Development and Differentiation 92
VI. Roles of Protein Arginine Methyltransferases in Disease 96
VII. Conclusions and Future Directions 99
Structure of Protein Arginine Methyltransferases1 117
I. Abstract 117
II. Protein Arginine Methylation 118
III. PRMT1 122
IV. CARM1/PRMT4 123
V. A Conserved PRMT Core 123
VI. Structure of the Conserved PRMT Core 124
VII. PRMT Dimerization is Essential for AdoMet Binding and Enzymatic Activity 124
VIII. Multiple Substrate Binding Grooves 126
IX. Asymmetric and Symmetric Dimethylarginines 126
X. Antagonize Arginine Methylation 128
Methylation and Demethylation of Histone Arg and Lys Residues in Chromatin Structure and Function 135
I. Abstract 135
II. Introduction 136
III. Chromatin Structure and Function 136
IV. Histone Lys Methylation 139
V. Histone Lys Demethylase 148
VI. Histone Arg Methylation and Transcription 150
VII. Histone Arg Demethylating Enzymes 153
VIII. Conclusions 159
Structure of SET Domain Protein Lysine Methyltransferases 167
I. Abstract 167
II. Introduction 168
III. SET Domains in Context 172
IV. Overall Structure 173
V. Structure of the N- and C-Flanking Domains 175
VI. The Cofactor Binding Site 177
VII. Substrate Binding 177
VIII. Active Site and Methylation 181
IX. Flexibility of the C-Flanking Domain 183
Non-Histone Protein Lysine Methyltransferases: Structure and Catalytic Roles 191
I. Abstract 191
II. Introduction 192
III. Diversity of Polypeptide Substrates 199
IV. Non-Histone Protein Methyltransferases 203
V. Conclusions and Future Prospects 226
Demethylation Pathways for Histone Methyllysine Residues 241
I. Abstract 241
II. Introduction 242
III. Histone Demethylation by LSD1 Is a Flavin- Dependent Oxidative Process 243
IV. LSD1 Is Part of Many Multiprotein Corepressor Complexes 247
V. Other Proposed Mechanisms for Histone Lysine Demethylation 248
VI. Conclusions 250
Biological Regulation by Protein Methyl Ester Formation 255
Structure and Function of Isoprenylcysteine Carboxylmethyltransferase (Icnt): A Key Enzyme in CaaX Processing 257
I. Abstract 257
II. Introduction 258
III. Characterization of Icmt Proteins 260
IV. Cellular Functions of Icmts: Use of Small Molecules to Probe Icmt Function 271
V. Development of Novel Small-Molecule Icmt Inhibitors 272
Genetic Approaches to Understanding the Physiologic Importance of the Carboxyl Methylation of Isoprenylated Proteins 285
I. Abstract 285
II. Introduction 286
III. STE14 from S. cerevisiae 287
IV. Biochemical Studies of Icmt Function in Mammals 289
V. Inactivating kmt in Mouse Embryonic Stem Cells 291
VI. lcmt Knockout Mice 293
VII. Altered Electrophoretic Mobility of Ras Proteins in lcmt Fibroblasts 295
VIII. Mislocalization of Ras Proteins in lcmt Fibroblasts 296
IX. Impact of Methylation on the Binding of K- Ras to Microtubules 298
X. Icmt is AlsoResponsible for Methylating the CXC Rab Proteins 299
XI. Assessing the Impact of lcmt Deficiency on Ras Transformation 299
XII. An Effect of lcmt Deficiency on Prelamin A Processing 305
XIII. Pharmacologic Inhibition of Icmt 307
Reversible Methylation of Protein Phosphatase 2A 315
I. Abstract 315
II. PP2A Can Be Reversibly Methylated on Its C- terminal Leucine Residue: The Discovery 316
III. Methylation of PP2A by a Leucine Carboxyl Methyltransferase ( LCMT1) 317
IV. PP2A-methylesterase (PME-1) 324
V. The PP2A-PME-PTPA Interplay 325
VI. Regulation of PP2A Methylation 326
VII. Conclusions and Perspectives 329
Reversible Methylation of Glutamate Residues in the Receptor Proteins of Bacterial Sensory Systems 337
I. Abstract 337
II. Introduction 338
III. The Signaling Pathway 339
IV. The Methyltransferase and Its Substrate 348
V. Conclusions 379
Recognition of Damaged Proteins in Aging by Protein Methyltransferases 395
Protein L-Isoaspartyl, D-Aspartyl Methyltransferases: Catalysts for Protein Repair 397
I. Abstract 397
II. Introduction 398
III. Biochemistry of PIMT-Catalyzed Reactions 399
IV. Crystallographic Studies of PIMTs 408
V. Phylogenetic Distribution of PIMT Activities Deduced from Whole Genome Sequences 411
VI. Biochemistry of Protein Isoaspartyl Methylation In Vivo 412
VII. Accumulation of Isoaspartyl and Racemized Proteins During Aging 420
VIII. Physiological Studies of PIMT Function 423
Modification of Proteins by Methylation of Glutamine and Asparagine Residues 447
Modification of Glutamine Residues in Proteins Involved in Translation 449
I. Abstract 449
II. Introduction 450
III. Ribosomal Protein Methylation 451
IV. Biological Significance: The Role of Methylated Release Factors 459
V. The Extended Gln MTase Family 462
VI. Conclusions 463
Modification of Phycobiliproteins at Asparagine Residues 467
I. Abstract 467
II. Introduction 467
III. Occurrence 468
IV. Biochemistry 470
V. Potential Functions 471
VI. Deamidation 471
VII. Protein Stability 472
VIII. Specialized Energy Transfer 472
IX. Conclusions 473
Inhibition of Methyltransferases by Metabolites 477
Inhibition of Mammalian Protein Methyltransferases by 5'- Methylthioadenosine ( MTA): A Mechanism of Action of Dietary SAMe? 479
I. Abstract 479
II. Introduction 480
III. Formation and Metabolism of MTA in Mammalian Cells 481
IV. Usefulness of MTA as a Reagent to Inhibit Protein Methylation in Intact Cells: Mechanism of Action 482
V. Pharmaceutical AdoMet (SAMe) as an Extracellular Time- Release Form of MTA, Resulting in the Inhibition of Intracellular Methyltransferases? 485
VI. Effects of MTA on Cellular Functions and Correlation with Effects on Specific Protein Methyltransferases 488
VII. Biochemical Actions of AdoMet/MTA Not Involving Methyltransferases 495
VIII. Effects of Dietary AdoMet Not Mediated by Either AdoMet or MTA: Role of Adenosine? 497
IX. Conclusions 497
Author Index 507
Index 567
Color Plate 583

Produkt-Details

• Erscheint lt. Verlag: 21.9.2011
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Chemie
• Themenwelt: Naturwissenschaften ► Physik / Astronomie ► Angewandte Physik
• Themenwelt: Technik
• ISBN-10: 0-08-046042-9 / 0080460429
• ISBN-13: 978-0-08-046042-0 / 9780080460420