S-Adenosylmethionine-Dependent Methyltransferases : Structures and Functions

by Cheng, Xiaodong; Blumenthal, Robert M.

• ISBN13: 9789810238704
• ISBN10: 9810238703
• Format: Hardcover
• Copyright: 2000-07-01
• Publisher: World Scientific Pub Co Inc

Summary

This invaluable volume, written by an international group of scientists, presents an overview of the AdoMet-dependent methyltransferases, with special emphasis on structure-function relationships.S-adenosyl-L-methionine (AdoMet) is the second most commonly used enzyme cofactor after ATP. The AdoMet-dependent methyltransferases act on a wide variety of target molecules, including DNA, RNA, protein, polysaccharides, lipids and a range of small molecules.The well-conserved architecture of these enzymes, and the implications of this conservation for their evolutionary history, are major themes of this book. The thirteen chapters describe in detail the structures, enzyme kinetics and biological roles of the AdoMet-dependent methyltransferases from a wide range of cell types: plant, animal, bacterial and archaeal.

Table of Contents

Structure and Evolution of AdoMet-Dependent Methyltransferases	1	(38)
Eric B. Fauman
Robert M. Blumenthal
Xiaodong Cheng
Introduction: chemistry of AdoMet-dependent methyltransfer	1	(7)
AdoMet is a very commonly-used cofactor	1	(2)
Various types of Ado-Met-dependent methylation	3	(3)
Chemistry of methylating different atoms	6	(2)
A common architecture for AdoMet-dependent MTases	8	(12)
Almost all examples solved to date share a common core	8	(7)
AdoMet binding	15	(2)
Conserved amino acid sequence motifs	17	(3)
A relationship between the AdoMet-dependent MTases and the Rossmann fold proteins	20	(5)
The overall architecture of AdoMet-dependent MTases is strikingly similar to that of the eight known families of Rossmann fold proteins	20	(1)
The positions of the adenosine moieties of Rossmann fold proteins are exactly analogous to the positions of the AdoMet adenosine moieties in the MTases	21	(2)
Catalytically-active sidechains occupy some analogous and some distinct positions in AdoMet-dependent MTases and Rossmann fold proteins	23	(1)
Did the MTases arise from gene duplication?	24	(1)
Classification of MTases: overall sequence similarity vs. motif order	25	(2)
Structure-guided alignments reveal a low degree of overall sequence conservation	25	(1)
Variation in linear motif order among MTases	25	(2)
Does the structural conservation among AdoMet-dependent MTases reflect divergent or convergent evolution?	27	(3)
Criteria for distinguishing divergent from convergent evolution	27	(2)
Divergence of the β family of DNA MTases might be explained by derivation from a circularly-permuted RNA MTase	29	(1)
Conclusions and future work	30	(1)
Acknowledgements	30	(9)
References	32	(7)
The Black Sheep of the Family: AdoMet-Dependent Methyltransferases that do not Fit the Consensus Structural Fold	39	(16)
Melinda M. Dixon
Eric Fauman
Martha L. Ludwig
Introduction	39	(1)
Reactivation domain of cobalamin-dependent methionine synthase (MetH)	40	(6)
Role of the MetH reactivation domain	40	(3)
Structure of MetH reactivation domain	43	(1)
Conformation and interactions of AdoMet in the MetH reactivation domain	44	(1)
Reaction with the cobalamin-binding domain	45	(1)
Precorrin MTase CbiF	46	(4)
Role of CbiF	46	(1)
Structure of CbiF	46	(2)
Interactions and conformation of AdoHcy bound to CbiF	48	(2)
AdoMet/AdoHcy binding in catechol-O-MTase, MetH and CbiF	50	(1)
Perspectives	51	(1)
Acknowledgements	52	(3)
References	52	(3)
Catechol O-Methyltransferase	55	(38)
Jukka Vidgren
Martti Ovaska
Jukka Tenhunen
Carola Tilgmann
Timo Lotta
Pekka T. Mannisto
Introduction	55	(1)
S-COMTase and MB-COMTase enzyme forms	56	(1)
Distribution of COMTase proteins in mammalian tissues	57	(1)
Subcellular localization of COMTase proteins	58	(2)
COMTase gene	60	(3)
Structure of COMTase gene	60	(1)
Regulation of COMTase expression	61	(1)
Genetic polymorphism of human COMTase	61	(2)
Enzyme kinetic mechanisms	63	(2)
Kinetics of COMTase polymorphs with different thermostability	64	(1)
Crystal structures of COMTase	65	(7)
Structure of COMTase complexed with AdoMet, 3,5-dinitrocatechol and magnesium	66	(1)
The active site --- AdoMet binding and magnesium binding	66	(3)
Binding of catechol-like structures of COMTase	69	(1)
Species-related active site differences	69	(1)
Structure of COMTase complexed with OR-1840	70	(2)
Reaction mechanism of the methyltransfer catalyzed by COMTase	72	(3)
Inhibition of the COMTase enzyme	75	(2)
New COMTase inhibitors	75	(2)
Inhibition mechanism of nitrocatechol-type inhibitors	77	(1)
Practical clinical applications and theoretical indications of COMTase inhibitors	77	(16)
COMTase inhibitors as an aid in positron emission tomography (PET)	79	(1)
References	80	(13)
Glycine N-Methyltransferase, A Tetrameric Enzyme	93	(30)
Fusao Takusagawa
Hirofumi Ogawa
Motoji Fujioka
Introduction	93	(1)
GNMTase	94	(7)
Physicochemical properties of rat liver GNMTase	95	(1)
Amino acid sequence of GNMTase	95	(1)
Kinetic properties of GNMTase	96	(4)
Inactivation of GNMTase by chemical modification	100	(1)
Crystal structure of rat GNMTase	101	(10)
Tetramer structure	102	(2)
AdoMet binding site	104	(2)
Chemical mechanism of GNMTase reaction	106	(3)
Folate binding to GNMTase	109	(2)
Comparison to the structure and function of AdoHcy hydrolase	111	(3)
Relationship between GNMTase and AdoHcy hydrolase	112	(2)
Tissue and subcellular localization, and physiological role of GNMTase	114	(3)
Future work	117	(6)
References	119	(4)
A Protein Carboxyl Methyltransferase that Recognizes Age-Damaged Peptides and Proteins and Participates in their Repair	123	(26)
Steven Clarke
Introduction	123	(1)
Distribution of the L-isoaspartyl MTase in nature	124	(3)
Structure of the L-isoaspartyl MTases	127	(4)
Genes specifying L-isoaspartyl MTases	127	(1)
Diversity of mammalian enzymes due to alternative splicing of transcripts and gene polymorphisms	128	(1)
Enzyme structure and localization	129	(1)
Availability of purified enzymes	129	(1)
Three-dimensional structural studies	129	(2)
Substrate specificity of the MTase	131	(3)
Are some proteins more prone to isomerization and racemization than others?	132	(1)
Alternative sources of L-isoaspartate residues in proteins	132	(2)
Repair pathways	134	(2)
Repair of D-aspartate residues?	134	(1)
Repair of extracellular proteins?	134	(1)
Self-repair of L-isoaspartyl MTase	135	(1)
Defective repair in human diseases	135	(1)
A role for repair in proteolysis?	135	(1)
Gene knockout model systems for studying the physiological role of the L-isoaspartyl MTase	136	(3)
Bacteria	136	(1)
Yeast	137	(1)
Worms	137	(1)
Flies	138	(1)
Amphibians	138	(1)
Mice	138	(1)
Plants	139	(1)
Future work	139	(1)
Acknowledgements	139	(10)
References	140	(9)
Protein Methyltransferases Involved in Signal Transduction	149	(36)
Snezana Djordjevic
Ann M. Stock
Ying Chen
Jeffry B. Stock
Introduction	149	(1)
Bacterial Receptor MTases	150	(10)
Receptor methylation	150	(2)
Structure of MTase CheR	152	(2)
MTase-receptor interactions	154	(5)
Sequence analysis	159	(1)
Prenylcysteine MTases	160	(6)
CAAX-tail processing	160	(2)
Enzymology of the prenylcysteine methylation system	162	(3)
Prenylcysteine MTase substrates and inhibitors	165	(1)
Function of prenylcysteine methylation	165	(1)
Phosphoprotein phosphatase 2A MTases	166	(2)
Phosphoprotein phosphatase 2A	166	(1)
PP2A MTase	167	(1)
PP2A methylesterase	168	(1)
Protein arginine MTases	168	(4)
Arginine methylation	168	(2)
Involvement in signaling	170	(2)
Sequence analysis	172	(1)
Acknowledgements	172	(13)
References	173	(12)
tRNA Methyltransferases	185	(14)
Walter M. Holmes
Introduction	185	(1)
Biological function	185	(1)
Classes of enzyme	186	(7)
tRNA 5mU54 MTase (RUMT)	187	(2)
tRNA N1mG MTase (1MGT)	189	(3)
tRNA mG18 2'-O-MTase	192	(1)
tRNA 5mC MTase	192	(1)
tRNA N1mA58 MTase	193	(1)
tRNA N2,2mG26 MTase	193	(1)
Summary and Conclusions	193	(6)
References	194	(5)
rRNA Methyltransferases (ErmC' and ErmAM) and Antibiotic Resistance	199	(28)
Cele Abad-Zapatero
Ping Zhong
Dirksen E. Bussiere
Kent Steward
Steven W. Muchmore
Introduction	199	(2)
MTases involved in rRNA processing and maturation	201	(3)
General considerations about rRNA MTases	201	(1)
rRNA MTases modifying ribose sugars	202	(1)
rRNA MTases modifying nucleotide bases	203	(1)
rRNA MTases involved in antibiotic resistance	204	(10)
General considerations	204	(1)
Macrolide-Lincosamide and streptogramin-B resistance: Erm rRNA MTases	205	(1)
Structures of ErmC' and ErmAM	206	(2)
Consensus structure of the Erm family of rRNA MTases	208	(1)
Structural relation to N6mA DNA MTases	208	(2)
AdoMet binding	210	(1)
rRNA recognition	211	(3)
Structure-guided amino acid sequence comparisons among rRNA MTases	214	(4)
tRNA MTases	217	(1)
Conclusions and future work	218	(1)
Acknowledgements	218	(9)
References	218	(9)
Nucleoside Methylation in Eukaryotic mRNA: HeLa mRNA (N6-Adenosine)-Methyltransferase	227	(28)
Joseph A. Bokar
Fritz M. Rottman
Introduction	227	(1)
Methylated nucleosides present in eukaryotic mRNA --- the 5'-terminal cap structure	227	(2)
Biological function of methylated nucleosides within the cap structure	228	(1)
Enzymes involved in cap methylation	228	(1)
Modified nucleosides at internal positions in eukaryotic mRNA	229	(6)
N6mA	230	(1)
Sequence specific distribution of N6mA in vivo	231	(1)
Function of N6mA in mRNA	232	(1)
Mutation of N6mA sites	232	(1)
Studies utilizing methylation inhibitors	233	(2)
Characterization and purification of HeLa mRNA N6mA MTase	235	(12)
Sequence specificity in vitro	235	(2)
Purification of HeLa mRNA N6mA MTase	237	(1)
Purification and cDNA cloning of the AdoMet-binding subunit	238	(1)
GenBank and Expressed Sequence Tag (EST) database homology searches	238	(6)
Northern blot analysis of MT-A70 expression	244	(1)
Subnuclear localization of MT-A70 in HeLa Cells	245	(1)
Further characterization of MT-B	246	(1)
Conclusion	247	(8)
References	247	(8)
VP39---An mRNA Cap-Specific 2'-O-Methyltransferase	255	(28)
Alec E. Hodel
Florante A. Quiocho
Paul D. Gershon
Introduction	255	(2)
mRNA biogenesis: outline of terminal processing steps	255	(1)
Vaccinia as an enzymological tool	256	(1)
Vaccinia protein VP39 --- a nucleic acid ribose MTase and a poly(A) polymerase processivity factor	256	(1)
VP39 overall architecture and evolution	257	(2)
Architecture	257	(1)
Relationship to other AdoMet-dependent MTases	258	(1)
Cofactor	259	(3)
AdoMet binding mutants	259	(2)
VP39-AdoMet interactions	261	(1)
AdoMet-binding mutant phenotypes in a structural context	262	(1)
N7mG moiety of the mRNA cap	262	(8)
Specificity	262	(1)
Cap-dependent RNA binding assay based on surface plasmon resonance	263	(1)
N7mG-binding pocket	264	(1)
VP39-N7mG interactions	264	(1)
Reconciling the mutagenesis and crystallography	265	(1)
How does VP39 discriminate 7-methylated from unmethylated G?	266	(2)
How might the Y22/F180 stacking sandwich favor 7-methylated over unmethylated G?	268	(1)
By what biophysical mechanism might the positively charged N7mG base enhance stacking?	268	(1)
Adenine-cap binding to the N7mG pocket in the context of capped RNA	269	(1)
Hydrogen-bonding to N7mG	269	(1)
MTase-specific VP39-RNA interactions: A four-site model for VP39-substrate interaction	270	(5)
Downstream RNA-binding cleft	270	(2)
VP39-phosphoribose backbone interactions within minimal MTase substrates	272	(1)
pH-dependent binding of the first RNA trimer	273	(2)
A distal downstream RNA-binding site?	275	(1)
Basic enzymology and possible catalytic mechanism	275	(2)
Interaction between VP39's two functions	277	(1)
Conclusions and future work	278	(5)
References	279	(4)
Bacterial DNA Methyltransferases	283	(58)
David T. F. Dryden
Introduction	283	(2)
The DNA MTases	283	(1)
Base flipping	283	(1)
Scope of this chapter	284	(1)
Biology of DNA MTases	285	(3)
Dam and Dcm MTases	285	(1)
R/M systems	286	(1)
Antirestriction MTases	287	(1)
Structural domains	288	(7)
Target recognition domains (TRDs)	288	(3)
AdoMet binding and catalytic domain	291	(1)
Other domain structures	291	(1)
Endonuclease DNA cleavage domains	292	(1)
DNA helicase domains	293	(2)
Classification of DNA MTases	295	(11)
Type II R/M systems	295	(1)
Type IIs R/M systems	296	(1)
Multifunctional MTases	296	(1)
Type I R/M system	296	(1)
Specificity (S) subunits	297	(3)
Modification (M) subunits	300	(1)
Restriction (R) subunits	301	(1)
Type I 1/2 R/M systems	302	(1)
BcgI-like R/M systems	302	(1)
Type III R/M systems	303	(1)
Type IV R/M systems	304	(1)
Assembly of DNA MTases	305	(1)
Chemical reactions of DNA MTases	306	(4)
5mC methylation	306	(2)
N4mC and N6mA methylation	308	(1)
Kinetics of DNA methylation	309	(1)
Physical mechanism	310	(9)
Locating the DNA target sequence	310	(1)
DNA binding affinity	311	(2)
DNA footprinting	313	(1)
Type II MTases	313	(1)
DNA bending by type II MTases	313	(1)
Footprinting of type I R/M enzymes	314	(1)
Substrate-induced conformational changes in DNA MTases	314	(1)
Crystallographic evidence	314	(1)
Limited proteolysis of MTases	315	(1)
Spectroscopic methods	316	(1)
Hydrodynamic measurements	316	(1)
Conformational changes in the DNA and nucleotide base flipping	317	(2)
Mechanism of EcoRI N6mA MTase	319	(1)
Summary	319	(2)
Acknowledgements	321	(20)
References	321	(20)
Eukaryotic DNA Methyltransferases	341	(32)
Paula M. Vertino
Introduction	341	(1)
Establishment of genome methylation patterns	341	(2)
Enzymology of Eukaryotic MTases	343	(2)
Eukaryotic DNA MTase families	345	(4)
Dnmt1 family MTases	349	(8)
Substrate selectivity	351	(2)
Dnmt1: single gene or multigene family?	353	(1)
Maintenance methylation and DNA replication	354	(2)
De novo methylation by Dnmt1	356	(1)
Dnmt2 family MTases	357	(2)
Yeast DNA MTases?: pmt1	358	(1)
Masc-1 family DNA MTases	359	(1)
Dnmt3 family MTases	359	(1)
MTases and chromatin structure: TrxG/PcG proteins, methylated DNA binding proteins and chromomethylases	360	(1)
Conclusion	361	(1)
Acknowledgements	362	(11)
References	362	(11)
Mechanisms of DNA Demethylation in Vertebrates	373	(20)
Jean-Pierre Jost
Edward J. Oakeley
Steffen Schwarz
Introduction	373	(1)
DNA methylation/demethylation and the formation of methylation patterns	374	(1)
Passive demethylation	375	(3)
Natural inhibitors of DNA MTase	376	(1)
Nucleotide analogs as inhibitors of DNA methylation	376	(1)
Passive demethylation by drugs influencing the level of AdoMet	377	(1)
Active demethylation	378	(5)
Indirect evidence for the presence of an active DNA demethylation system	378	(1)
Direct evidence for active DNA demethylation	379	(1)
5mC-DNA glycosylase	380	(1)
The activity of 5mC-DNA glycosylase requires both protein and RNA	381	(1)
RNA alone is causing DNA demethylation	382	(1)
Cis-trans regulatory elements of DNA demethylation	383	(1)
Sequence of events leading to site specific demethylation of the avian vitellogenin gene	384	(1)
Conclusions and future work	385	(1)
Acknowledgements	385	(8)
References	385	(8)
Appendix I	393	(5)
Appendix II	398