DB code: S00262

RLCP classification	3.747.6310.11 : Transfer
CATH domain	3.40.50.150 : Rossmann fold	Catalytic domain
E.C.	2.1.1.113
CSA	1boo
M-CSA	1boo
MACiE

CATH domain	Related DB codes (homologues)
3.40.50.150 : Rossmann fold	S00637 S00639 S00261 S00291 S00412 D00075 D00076 D00079 D00080 D00082 D00083 D00823

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	Pfam
P11409	Modification methylase PvuII	M.PvuII EC 2.1.1.113 N-4 cytosine-specific methyltransferase PvuII	PF01555 (N6_N4_Mtase) [Graphical View]

KEGG enzyme name
site-specific DNA-methyltransferase (cytosine-N4-specific) modification methylase restriction-modification system DNA[cytosine-N4]methyltransferase m4C-forming MTase S-adenosyl-L-methionine:DNA-cytosine 4-N-methyltransferase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P11409	MTP2_PROVU	S-adenosyl-L-methionine + DNA cytosine = S- adenosyl-L-homocysteine + DNA N(4)-methylcytosine.

KEGG Pathways
Map code	Pathways	E.C.

Compound table
	Substrates		Products		Intermediates
KEGG-id	C00019	C00856	C00021	C03110
E.C.
Compound	S-Adenosyl-L-methionine	DNA cytosine	S-Adenosyl-L-homocysteine	DNA N4-methylcytosine
Type	amino acids,amine group,nucleoside,sulfonium ion	amine group,nucleic acids	amino acids,amine group,nucleoside,sulfide group	amine group,nucleic acids
ChEBI	67040 67040		16680 57856 16680 57856
PubChem	34755 34755		25246222 439155 25246222 439155

1booA	Unbound	Unbound	Bound:SAH	Unbound

Reference for Active-site residues
resource	references	E.C.
literature [2]

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1booA	SER 53;ASP 96

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[2]	Figure 6a, p.2711	1

References
[1]
Resource
Comments
Medline ID
PubMed ID	2690017
Journal	Nucleic Acids Res
Year	1989
Volume	17
Pages	10403-25
Authors	Kaszubska W, Aiken C, O'Connor CD, Gumport RI
Title	Purification, cloning and sequence analysis of RsrI DNA methyltransferase: lack of homology between two enzymes, RsrI and EcoRI, that methylate the same nucleotide in identical recognition sequences.
Related PDB
Related UniProtKB
[2]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS)
Medline ID	97351137
PubMed ID	9207015
Journal	Nucleic Acids Res
Year	1997
Volume	25
Pages	2702-15
Authors	Gong W, O'Gara M, Blumenthal RM, Cheng X
Title	Structure of pvu II DNA-(cytosine N4) methyltransferase, an example of domain permutation and protein fold assignment.
Related PDB	1boo
Related UniProtKB	P11409
[3]
Resource
Comments
Medline ID
PubMed ID	9288926
Journal	Eur J Biochem
Year	1997
Volume	247
Pages	1009-18
Authors	O'Gara M, Adams GM, Gong W, Kobayashi R, Blumenthal RM, Cheng X
Title	Expression, purification, mass spectrometry, crystallization and multiwavelength anomalous diffraction of selenomethionyl PvuII DNA methyltransferase (cytosine-N4-specific).
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	9204874
Journal	Biochemistry
Year	1997
Volume	36
Pages	8284-92
Authors	Adams GM, Blumenthal RM
Title	The PvuII DNA (cytosine-N4)-methyltransferase comprises two trypsin-defined domains, each of which binds a molecule of S-adenosyl-L-methionine.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	10651285
Journal	Proteins
Year	1999
Volume	37
Pages	717-28
Authors	Radlinska M, Bujnicki JM, Piekarowicz A
Title	Structural characterization of two tandemly arranged DNA methyltransferase genes from Neisseria gonorrhoeae MS11: N4-cytosine specific M.NgoMXV and nonfunctional 5-cytosine-type M.NgoMorf2P.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	9927736
Journal	Nucleic Acids Res
Year	1999
Volume	27
Pages	1032-8
Authors	Rice MR, Koons MD, Blumenthal RM
Title	Substrate recognition by the Pvu II endonuclease: binding and cleavage of CAG5mCTG sites.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	10329711
Journal	J Biol Chem
Year	1999
Volume	274
Pages	15066-72
Authors	Holz B, Dank N, Eickhoff JE, Lipps G, Krauss G, Weinhold E
Title	Identification of the binding site for the extrahelical target base in N6-adenine DNA methyltransferases by photo-cross-linking with duplex oligodeoxyribonucleotides containing 5-iodouracil at the target position.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	9931007
Journal	Biochemistry
Year	1999
Volume	38
Pages	1426-34
Authors	Pues H, Bleimling N, Holz B, Wolcke J, Weinhold E
Title	Functional roles of the conserved aromatic amino acid residues at position 108 (motif IV) and position 196 (motif VIII) in base flipping and catalysis by the N6-adenine DNA methyltransferase from Thermus aquaticus.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	11024175
Journal	Nucleic Acids Res
Year	2000
Volume	28
Pages	3950-61
Authors	Scavetta RD, Thomas CB, Walsh MA, Szegedi S, Joachimiak A, Gumport RI, Churchill ME
Title	Structure of RsrI methyltransferase, a member of the N6-adenine beta class of DNA methyltransferases.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	11405235
Journal	Biol Chem
Year	2001
Volume	382
Pages	707-10
Authors	Jeltsch A
Title	The cytosine N4-methyltransferase M.PvuII also modifies adenine residues.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID	12507474
Journal	J Mol Biol
Year	2003
Volume	325
Pages	711-20
Authors	Lindstrom WM Jr, Malygin EG, Ovechkina LG, Zinoviev VV, Reich NO
Title	Functional analysis of BamHI DNA cytosine-N4 methyltransferase.
Related PDB
Related UniProtKB

Comments
According to the literature [2], the reaction proceeds as follows: (1) Asp96 may act as a general base to activate the N4 amino group, the cytosine acceptor group through the Ser53 (as a proton shuttle). (Ser53 and Asp96 seem to belong to a charge relay system, which is analogous to that seen in the serine proteases.) (2) At the next step, the activated cytosine N4 atom makes a nucleophilic attack on the AdoMet methyl group, resulting in the formation of the methylated cytosine product.

Comments

According to the literature [2], the reaction proceeds as follows:
(1) Asp96 may act as a general base to activate the N4 amino group, the cytosine acceptor group through the Ser53 (as a proton shuttle). (Ser53 and Asp96 seem to belong to a charge relay system, which is analogous to that seen in the serine proteases.)
(2) At the next step, the activated cytosine N4 atom makes a nucleophilic attack on the AdoMet methyl group, resulting in the formation of the methylated cytosine product.

Created	Updated
2002-11-22	2009-02-26