MTH1_HAEPH
ID MTH1_HAEPH Reviewed; 327 AA.
AC P05102;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Type II methyltransferase M.HhaI {ECO:0000303|PubMed:12654995};
DE Short=M.HhaI {ECO:0000303|PubMed:8506140};
DE EC=2.1.1.37 {ECO:0000269|PubMed:7899082};
DE AltName: Full=Cytosine-specific methyltransferase HhaI;
DE AltName: Full=Modification methylase HhaI;
GN Name=hhaIM;
OS Haemophilus parahaemolyticus.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC Pasteurellaceae; Haemophilus.
OX NCBI_TaxID=735;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 10014 / CCUG 3716 / NCTC 8479 / 536;
RX PubMed=3549710; DOI=10.1016/s0021-9258(18)61262-1;
RA Caserta M., Zacharias W., Nwankwo D.O., Wilson G.G., Wells R.D.;
RT "Cloning, sequencing, in vivo promoter mapping, and expression in
RT Escherichia coli of the gene for the HhaI methyltransferase.";
RL J. Biol. Chem. 262:4770-4777(1987).
RN [2]
RP FUNCTION, MUTAGENESIS OF CYS-81, DNA-BINDING, AND ACTIVE SITE.
RX PubMed=8506140; DOI=10.1093/nar/21.10.2459;
RA Mi S., Roberts R.J.;
RT "The DNA binding affinity of HhaI methylase is increased by a single amino
RT acid substitution in the catalytic center.";
RL Nucleic Acids Res. 21:2459-2464(1993).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF GLN-237.
RX PubMed=7899082; DOI=10.1093/nar/23.4.620;
RA Mi S., Alonso D., Roberts R.J.;
RT "Functional analysis of Gln-237 mutants of HhaI methyltransferase.";
RL Nucleic Acids Res. 23:620-627(1995).
RN [4]
RP NOMENCLATURE.
RX PubMed=12654995; DOI=10.1093/nar/gkg274;
RA Roberts R.J., Belfort M., Bestor T., Bhagwat A.S., Bickle T.A.,
RA Bitinaite J., Blumenthal R.M., Degtyarev S.K., Dryden D.T., Dybvig K.,
RA Firman K., Gromova E.S., Gumport R.I., Halford S.E., Hattman S.,
RA Heitman J., Hornby D.P., Janulaitis A., Jeltsch A., Josephsen J., Kiss A.,
RA Klaenhammer T.R., Kobayashi I., Kong H., Krueger D.H., Lacks S.,
RA Marinus M.G., Miyahara M., Morgan R.D., Murray N.E., Nagaraja V.,
RA Piekarowicz A., Pingoud A., Raleigh E., Rao D.N., Reich N., Repin V.E.,
RA Selker E.U., Shaw P.C., Stein D.C., Stoddard B.L., Szybalski W.,
RA Trautner T.A., Van Etten J.L., Vitor J.M., Wilson G.G., Xu S.Y.;
RT "A nomenclature for restriction enzymes, DNA methyltransferases, homing
RT endonucleases and their genes.";
RL Nucleic Acids Res. 31:1805-1812(2003).
RN [5] {ECO:0007744|PDB:1HMY}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE, AND SUBUNIT.
RX PubMed=8343957; DOI=10.1016/0092-8674(93)90421-l;
RA Cheng X., Kumar S., Posfai J., Pflugrath J.W., Roberts R.J.;
RT "Crystal structure of the HhaI DNA methyltransferase complexed with S-
RT adenosyl-L-methionine.";
RL Cell 74:299-307(1993).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=8293469; DOI=10.1016/0092-8674(94)90342-5;
RA Klimasauskas S., Kumar S., Roberts R.J., Cheng X.;
RT "HhaI methyltransferase flips its target base out of the DNA helix.";
RL Cell 76:357-369(1994).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS).
RX PubMed=9207024; DOI=10.1093/nar/25.14.2773;
RA Kumar S., Horton J.R., Jones G.D., Walker R.T., Roberts R.J., Cheng X.;
RT "DNA containing 4'-thio-2'-deoxycytidine inhibits methylation by HhaI
RT methyltransferase.";
RL Nucleic Acids Res. 25:2773-2783(1997).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS).
RX PubMed=9783745; DOI=10.1038/2312;
RA O'Gara M., Horton J.R., Roberts R.J., Cheng X.;
RT "Structures of HhaI methyltransferase complexed with substrates containing
RT mismatches at the target base.";
RL Nat. Struct. Biol. 5:872-877(1998).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS).
RX PubMed=10080885; DOI=10.1006/jmbi.1999.2608;
RA O'Gara M., Zhang X., Roberts R.J., Cheng X.;
RT "Structure of a binary complex of HhaI methyltransferase with S-adenosyl-L-
RT methionine formed in the presence of a short non-specific DNA
RT oligonucleotide.";
RL J. Mol. Biol. 287:201-209(1999).
CC -!- FUNCTION: A methylase, recognizes the double-stranded sequence 5'-GCGC-
CC 3', methylates C-2 on both strands, and protects the DNA from cleavage
CC by the HhaI endonuclease. {ECO:0000269|PubMed:3549710,
CC ECO:0000269|PubMed:7899082, ECO:0000303|PubMed:12654995}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-
CC methyl-2'-deoxycytidine in DNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:13681, Rhea:RHEA-COMP:11369, Rhea:RHEA-COMP:11370,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:85452, ChEBI:CHEBI:85454; EC=2.1.1.37;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10018,
CC ECO:0000269|PubMed:7899082};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=69 nM for DNA {ECO:0000269|PubMed:7899082};
CC KM=15 nM for S-adenosyl-L-methionine (SAM)
CC {ECO:0000269|PubMed:7899082};
CC Vmax=87.0 nmol/min/mg enzyme {ECO:0000269|PubMed:7899082};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:8343957}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. C5-methyltransferase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01016}.
CC -!- CAUTION: Strain ATCC 10014 was originally thought to originate from
CC H.haemolyticus. {ECO:0000305}.
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DR EMBL; J02677; AAA24989.1; -; Genomic_DNA.
DR PIR; A26260; XYHIH1.
DR RefSeq; WP_005706946.1; NZ_MUXY01000011.1.
DR PDB; 10MH; X-ray; 2.55 A; A=1-327.
DR PDB; 1FJX; X-ray; 2.26 A; A=1-327.
DR PDB; 1HMY; X-ray; 2.50 A; A=1-327.
DR PDB; 1M0E; X-ray; 2.50 A; A=1-327.
DR PDB; 1MHT; X-ray; 2.60 A; A=1-327.
DR PDB; 1SKM; X-ray; 2.20 A; A=1-327.
DR PDB; 1SVU; X-ray; 2.66 A; A/B=1-327.
DR PDB; 2C7O; X-ray; 1.90 A; A=1-327.
DR PDB; 2C7P; X-ray; 1.70 A; A=1-327.
DR PDB; 2C7Q; X-ray; 1.85 A; A=1-327.
DR PDB; 2C7R; X-ray; 1.90 A; A=1-327.
DR PDB; 2HMY; X-ray; 2.61 A; B=1-327.
DR PDB; 2HR1; X-ray; 1.96 A; A=1-327.
DR PDB; 2I9K; X-ray; 2.65 A; A=1-327.
DR PDB; 2UYC; X-ray; 2.00 A; A=1-327.
DR PDB; 2UYH; X-ray; 2.63 A; A=1-327.
DR PDB; 2UZ4; X-ray; 2.10 A; A=1-327.
DR PDB; 2Z6A; X-ray; 2.88 A; A=1-327.
DR PDB; 2Z6Q; X-ray; 2.79 A; A=1-327.
DR PDB; 2Z6U; X-ray; 2.72 A; A=1-327.
DR PDB; 2ZCJ; X-ray; 2.75 A; A=1-327.
DR PDB; 3EEO; X-ray; 1.94 A; A=1-327.
DR PDB; 3MHT; X-ray; 2.70 A; A=1-327.
DR PDB; 4MHT; X-ray; 2.70 A; A=1-327.
DR PDB; 5CIY; X-ray; 1.59 A; A=1-327.
DR PDB; 5LOD; X-ray; 1.90 A; A/B=1-327.
DR PDB; 5MHT; X-ray; 2.70 A; A=1-327.
DR PDB; 6MHT; X-ray; 2.05 A; A=1-327.
DR PDB; 7MHT; X-ray; 2.87 A; A=1-327.
DR PDB; 8MHT; X-ray; 2.76 A; A=1-327.
DR PDB; 9MHT; X-ray; 2.39 A; A=1-327.
DR PDBsum; 10MH; -.
DR PDBsum; 1FJX; -.
DR PDBsum; 1HMY; -.
DR PDBsum; 1M0E; -.
DR PDBsum; 1MHT; -.
DR PDBsum; 1SKM; -.
DR PDBsum; 1SVU; -.
DR PDBsum; 2C7O; -.
DR PDBsum; 2C7P; -.
DR PDBsum; 2C7Q; -.
DR PDBsum; 2C7R; -.
DR PDBsum; 2HMY; -.
DR PDBsum; 2HR1; -.
DR PDBsum; 2I9K; -.
DR PDBsum; 2UYC; -.
DR PDBsum; 2UYH; -.
DR PDBsum; 2UZ4; -.
DR PDBsum; 2Z6A; -.
DR PDBsum; 2Z6Q; -.
DR PDBsum; 2Z6U; -.
DR PDBsum; 2ZCJ; -.
DR PDBsum; 3EEO; -.
DR PDBsum; 3MHT; -.
DR PDBsum; 4MHT; -.
DR PDBsum; 5CIY; -.
DR PDBsum; 5LOD; -.
DR PDBsum; 5MHT; -.
DR PDBsum; 6MHT; -.
DR PDBsum; 7MHT; -.
DR PDBsum; 8MHT; -.
DR PDBsum; 9MHT; -.
DR AlphaFoldDB; P05102; -.
DR BMRB; P05102; -.
DR SMR; P05102; -.
DR STRING; 735.B0185_07430; -.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR REBASE; 190421; M.Bce021ORF5376P.
DR REBASE; 3421; M.HhaI.
DR BRENDA; 2.1.1.37; 2531.
DR SABIO-RK; P05102; -.
DR EvolutionaryTrace; P05102; -.
DR PRO; PR:P05102; -.
DR GO; GO:0003886; F:DNA (cytosine-5-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0009307; P:DNA restriction-modification system; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR018117; C5_DNA_meth_AS.
DR InterPro; IPR001525; C5_MeTfrase.
DR InterPro; IPR031303; C5_meth_CS.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF00145; DNA_methylase; 1.
DR PRINTS; PR00105; C5METTRFRASE.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR00675; dcm; 1.
DR PROSITE; PS00094; C5_MTASE_1; 1.
DR PROSITE; PS00095; C5_MTASE_2; 1.
DR PROSITE; PS51679; SAM_MT_C5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Methyltransferase; Restriction system;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..327
FT /note="Type II methyltransferase M.HhaI"
FT /id="PRO_0000087882"
FT DOMAIN 12..325
FT /note="SAM-dependent MTase C5-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016"
FT ACT_SITE 81
FT /evidence="ECO:0000305|PubMed:7899082"
FT MUTAGEN 81
FT /note="C->G: Cells die, loss of methyltransferase activity,
FT binds DNA about 3-fold more tightly."
FT /evidence="ECO:0000269|PubMed:8506140"
FT MUTAGEN 81
FT /note="C->H: Cells grow as well as wild-type, loss of
FT methyltransferase activity, DNA affinity is about 20-fold
FT lower than wild-type."
FT /evidence="ECO:0000269|PubMed:8506140"
FT MUTAGEN 81
FT /note="C->R: Cells grow as well as wild-type, loss of
FT methyltransferase activity, DNA affinity is about 10-fold
FT lower than wild-type."
FT /evidence="ECO:0000269|PubMed:8506140"
FT MUTAGEN 81
FT /note="C->S: Cells grow as well as wild-type, loss of
FT methyltransferase activity, DNA affinity is about the same
FT as wild-type."
FT /evidence="ECO:0000269|PubMed:8506140"
FT MUTAGEN 237
FT /note="Q->X: Decrease in enzyme activity due to 98%-99%
FT loss of DNA-binding activity. No change in substrate
FT specificity."
FT /evidence="ECO:0000269|PubMed:7899082"
FT TURN 8..11
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:5CIY"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:2C7P"
FT HELIX 23..30
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 43..53
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 73..78
FT /evidence="ECO:0007829|PDB:5CIY"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:5CIY"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:9MHT"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 100..111
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 114..121
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 127..130
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 131..142
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 164..172
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 213..216
FT /evidence="ECO:0007829|PDB:1HMY"
FT STRAND 228..232
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 240..243
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:1SVU"
FT TURN 258..262
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 264..267
FT /evidence="ECO:0007829|PDB:5CIY"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 276..282
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 295..304
FT /evidence="ECO:0007829|PDB:5CIY"
FT HELIX 308..323
FT /evidence="ECO:0007829|PDB:5CIY"
SQ SEQUENCE 327 AA; 36996 MW; EF8A297E1DF819EB CRC64;
MIEIKDKQLT GLRFIDLFAG LGGFRLALES CGAECVYSNE WDKYAQEVYE MNFGEKPEGD
ITQVNEKTIP DHDILCAGFP CQAFSISGKQ KGFEDSRGTL FFDIARIVRE KKPKVVFMEN
VKNFASHDNG NTLEVVKNTM NELDYSFHAK VLNALDYGIP QKRERIYMIC FRNDLNIQNF
QFPKPFELNT FVKDLLLPDS EVEHLVIDRK DLVMTNQEIE QTTPKTVRLG IVGKGGQGER
IYSTRGIAIT LSAYGGGIFA KTGGYLVNGK TRKLHPRECA RVMGYPDSYK VHPSTSQAYK
QFGNSVVINV LQYIAYNIGS SLNFKPY
