MUTY_GEOSE
ID MUTY_GEOSE Reviewed; 366 AA.
AC P83847;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 2.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Adenine DNA glycosylase {ECO:0000303|PubMed:14961129, ECO:0000303|PubMed:25995449};
DE EC=3.2.2.31 {ECO:0000269|PubMed:19841264, ECO:0000269|PubMed:25995449};
DE AltName: Full=oxoG:A-specific adenine glycosylase {ECO:0000303|PubMed:25995449};
GN Name=mutY {ECO:0000303|PubMed:14961129};
OS Geobacillus stearothermophilus (Bacillus stearothermophilus).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Geobacillus.
OX NCBI_TaxID=1422;
RN [1]
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF MUTANT ASN-144 IN COMPLEXES WITH
RP DUPLEX DNA CONTAINING AN A:OXOG MISPAIR AND IRON-SULFUR (4FE-4S), FUNCTION,
RP AND COFACTOR.
RX PubMed=14961129; DOI=10.1038/nature02306;
RA Fromme J.C., Banerjee A., Huang S.J., Verdine G.L.;
RT "Structural basis for removal of adenine mispaired with 8-oxoguanine by
RT MutY adenine DNA glycosylase.";
RL Nature 427:652-656(2004).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 9-360 IN COMPLEX WITH IRON-SULFUR
RP (4FE-4S) AND DUPLEX DNA CONTAINING THE UNCLEAVABLE NUCLEOBASE
RP 2'-FLUORO-2'-DEOXYADENOSINE, CATALYTIC ACTIVITY, ACTIVE SITE, REACTION
RP MECHANISM, AND MUTAGENESIS OF GLU-43.
RX PubMed=19841264; DOI=10.1073/pnas.0902908106;
RA Lee S., Verdine G.L.;
RT "Atomic substitution reveals the structural basis for substrate adenine
RT recognition and removal by adenine DNA glycosylase.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:18497-18502(2009).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR (4FE-4S)
RP AND DUPLEX DNA.
RA O'Shea V.L., Cao S., Richards J.L., Horvath M.P., David S.S.;
RT "Structural illumination of a mutY glycosylase reaction coordinate
RT intermediate.";
RL Submitted (JAN-2009) to the PDB data bank.
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF WILD-TYPE AND MUTANT ASN-144 IN
RP COMPLEX WITH DUPLEX DNA CONTAINING AN OXOG:C BASE PAIR AND IRON-SULFUR
RP (4FE-4S), FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, COFACTOR,
RP AND MUTAGENESIS OF ASP-144.
RX PubMed=25995449; DOI=10.1074/jbc.m115.657866;
RA Wang L., Lee S.J., Verdine G.L.;
RT "Structural basis for avoidance of promutagenic DNA repair by MutY adenine
RT DNA glycosylase.";
RL J. Biol. Chem. 290:17096-17105(2015).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH DUPLEX DNA
RP CONTAINING AN A:OXOG MISPAIR AND IRON-SULFUR (4FE-4S).
RA Woods R.D., O'Shea V.L., Chu A., Cao S., Richards J.L., Horvath M.P.,
RA David S.S.;
RT "Structure and stereochemistry of the base excision repair glycosylase MutY
RT reveal a mechanism similar to retaining glycosidases.";
RL Submitted (SEP-2015) to the PDB data bank.
CC -!- FUNCTION: Base excision repair (BER) glycosylase that initiates repair
CC of A:oxoG to C:G by removing the inappropriately paired adenine base
CC from the DNA backbone, generating an abasic site product
CC (PubMed:25995449) (PubMed:14961129). 8-oxoguanine (oxoG) is a genotoxic
CC DNA lesion resulting from oxidation of guanine; this residue is misread
CC by replicative DNA polymerases, that insert adenine instead of cytosine
CC opposite the oxidized damaged base. Shows a powerful dicrimination of A
CC versus C, since it does not cleave cytosine in oxoG:C pairs
CC (PubMed:25995449). May also be able to remove adenine from A:G
CC mispairs, although this activity may not be physiologically relevant
CC (PubMed:14961129). {ECO:0000269|PubMed:25995449,
CC ECO:0000305|PubMed:14961129}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes free adenine bases from 7,8-dihydro-8-
CC oxoguanine:adenine mismatched double-stranded DNA, leaving an
CC apurinic site.; EC=3.2.2.31; Evidence={ECO:0000269|PubMed:19841264,
CC ECO:0000269|PubMed:25995449};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000305|PubMed:14961129, ECO:0000305|PubMed:25995449};
CC Note=Binds 1 [4Fe-4S] cluster (PubMed:14961129, PubMed:25995449). The
CC cluster has a structural role (PubMed:14961129).
CC {ECO:0000269|PubMed:14961129, ECO:0000269|PubMed:25995449};
CC -!- SIMILARITY: Belongs to the Nth/MutY family. {ECO:0000305}.
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DR RefSeq; WP_053414407.1; NZ_CP008934.1.
DR PDB; 1RRQ; X-ray; 2.22 A; A=1-365.
DR PDB; 1RRS; X-ray; 2.40 A; A=1-365.
DR PDB; 1VRL; X-ray; 2.50 A; A=1-365.
DR PDB; 3G0Q; X-ray; 2.20 A; A=9-360.
DR PDB; 4YOQ; X-ray; 2.21 A; A=1-365.
DR PDB; 4YPH; X-ray; 2.32 A; A=1-365.
DR PDB; 4YPR; X-ray; 2.59 A; A/B=1-365.
DR PDB; 5KN8; X-ray; 1.81 A; A=1-229.
DR PDB; 5KN9; X-ray; 1.93 A; A=1-229.
DR PDB; 6Q0C; X-ray; 2.00 A; A=1-365.
DR PDB; 6U7T; X-ray; 2.00 A; A=1-366.
DR PDBsum; 1RRQ; -.
DR PDBsum; 1RRS; -.
DR PDBsum; 1VRL; -.
DR PDBsum; 3G0Q; -.
DR PDBsum; 4YOQ; -.
DR PDBsum; 4YPH; -.
DR PDBsum; 4YPR; -.
DR PDBsum; 5KN8; -.
DR PDBsum; 5KN9; -.
DR PDBsum; 6Q0C; -.
DR PDBsum; 6U7T; -.
DR AlphaFoldDB; P83847; -.
DR SMR; P83847; -.
DR BRENDA; 3.2.2.31; 623.
DR EvolutionaryTrace; P83847; -.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0019104; F:DNA N-glycosylase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000701; F:purine-specific mismatch base pair DNA N-glycosylase activity; IEA:UniProtKB-EC.
DR GO; GO:0006284; P:base-excision repair; IDA:UniProtKB.
DR CDD; cd03431; DNA_Glycosylase_C; 1.
DR CDD; cd00056; ENDO3c; 1.
DR Gene3D; 1.10.1670.10; -; 1.
DR InterPro; IPR005760; A/G_AdeGlyc_MutY.
DR InterPro; IPR011257; DNA_glycosylase.
DR InterPro; IPR003651; Endonuclease3_FeS-loop_motif.
DR InterPro; IPR003265; HhH-GPD_domain.
DR InterPro; IPR023170; HhH_base_excis_C.
DR InterPro; IPR000445; HhH_motif.
DR InterPro; IPR044298; MIG/MutY.
DR InterPro; IPR029119; MutY_C.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR PANTHER; PTHR42944; PTHR42944; 1.
DR Pfam; PF00633; HHH; 1.
DR Pfam; PF00730; HhH-GPD; 1.
DR Pfam; PF14815; NUDIX_4; 1.
DR SMART; SM00478; ENDO3c; 1.
DR SMART; SM00525; FES; 1.
DR SUPFAM; SSF48150; SSF48150; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR TIGRFAMs; TIGR01084; mutY; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; DNA damage; DNA repair; DNA-binding; Glycosidase;
KW Hydrolase; Iron; Iron-sulfur; Metal-binding.
FT CHAIN 1..366
FT /note="Adenine DNA glycosylase"
FT /id="PRO_0000435340"
FT DOMAIN 105..133
FT /note="HhH"
FT /evidence="ECO:0000255"
FT ACT_SITE 43
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:19841264"
FT BINDING 30..31
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="substrate"
FT /ligand_part="adenine group"
FT /ligand_part_id="ChEBI:CHEBI:30756"
FT /ligand_part_note="mispaired A"
FT /evidence="ECO:0000269|PubMed:19841264"
FT BINDING 48..49
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="substrate"
FT /ligand_part="8-oxoguanine group"
FT /ligand_part_id="ChEBI:CHEBI:176966"
FT /evidence="ECO:0000269|PubMed:14961129,
FT ECO:0000269|PubMed:19841264"
FT BINDING 86..88
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="substrate"
FT /ligand_part="8-oxoguanine group"
FT /ligand_part_id="ChEBI:CHEBI:176966"
FT /evidence="ECO:0000269|PubMed:14961129,
FT ECO:0000269|PubMed:19841264"
FT BINDING 126
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="substrate"
FT /ligand_part="adenine group"
FT /ligand_part_id="ChEBI:CHEBI:30756"
FT /ligand_part_note="mispaired A"
FT /evidence="ECO:0000269|PubMed:19841264"
FT BINDING 188
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="substrate"
FT /ligand_part="adenine group"
FT /ligand_part_id="ChEBI:CHEBI:30756"
FT /ligand_part_note="mispaired A"
FT /evidence="ECO:0000269|PubMed:19841264"
FT BINDING 198
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:14961129,
FT ECO:0000269|PubMed:19841264, ECO:0000269|PubMed:25995449,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5, ECO:0007744|PDB:1RRQ,
FT ECO:0007744|PDB:1RRS, ECO:0007744|PDB:1VRL"
FT BINDING 205
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:14961129,
FT ECO:0000269|PubMed:19841264, ECO:0000269|PubMed:25995449,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5, ECO:0007744|PDB:1RRQ,
FT ECO:0007744|PDB:1RRS, ECO:0007744|PDB:1VRL"
FT BINDING 208
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:14961129,
FT ECO:0000269|PubMed:19841264, ECO:0000269|PubMed:25995449,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5, ECO:0007744|PDB:1RRQ,
FT ECO:0007744|PDB:1RRS, ECO:0007744|PDB:1VRL"
FT BINDING 214
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:14961129,
FT ECO:0000269|PubMed:19841264, ECO:0000269|PubMed:25995449,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.5, ECO:0007744|PDB:1RRQ,
FT ECO:0007744|PDB:1RRS, ECO:0007744|PDB:1VRL"
FT BINDING 308
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="substrate"
FT /ligand_part="8-oxoguanine group"
FT /ligand_part_id="ChEBI:CHEBI:176966"
FT /evidence="ECO:0000269|PubMed:14961129,
FT ECO:0000269|PubMed:19841264"
FT SITE 144
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000305|PubMed:19841264,
FT ECO:0000305|PubMed:25995449"
FT MUTAGEN 43
FT /note="E->Q: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:19841264"
FT MUTAGEN 144
FT /note="D->N: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:25995449"
FT HELIX 10..24
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 36..46
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 51..64
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 68..73
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 76..83
FT /evidence="ECO:0007829|PDB:5KN8"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:5KN9"
FT HELIX 89..105
FT /evidence="ECO:0007829|PDB:5KN8"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:4YPR"
FT HELIX 114..118
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 125..136
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 145..155
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 164..177
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 183..196
FT /evidence="ECO:0007829|PDB:5KN8"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 215..219
FT /evidence="ECO:0007829|PDB:5KN8"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:5KN8"
FT STRAND 236..246
FT /evidence="ECO:0007829|PDB:6Q0C"
FT STRAND 251..255
FT /evidence="ECO:0007829|PDB:6Q0C"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:6Q0C"
FT TURN 261..264
FT /evidence="ECO:0007829|PDB:6Q0C"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:6Q0C"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:6U7T"
FT HELIX 279..286
FT /evidence="ECO:0007829|PDB:6Q0C"
FT STRAND 293..296
FT /evidence="ECO:0007829|PDB:6Q0C"
FT STRAND 301..306
FT /evidence="ECO:0007829|PDB:6Q0C"
FT STRAND 311..322
FT /evidence="ECO:0007829|PDB:6Q0C"
FT STRAND 331..334
FT /evidence="ECO:0007829|PDB:6Q0C"
FT HELIX 336..341
FT /evidence="ECO:0007829|PDB:6Q0C"
FT HELIX 346..358
FT /evidence="ECO:0007829|PDB:6Q0C"
SQ SEQUENCE 366 AA; 41835 MW; 0D37855DFCF30C6B CRC64;
MTRETERFPA REFQRDLLDW FARERRDLPW RKDRDPYKVW VSEVMLQQTR VETVIPYFEQ
FIDRFPTLEA LADADEDEVL KAWEGLGYYS RVRNLHAAVK EVKTRYGGKV PDDPDEFSRL
KGVGPYTVGA VLSLAYGVPE PAVDGNVMRV LSRLFLVTDD IAKPSTRKRF EQIVREIMAY
ENPGAFNEAL IELGALVCTP RRPSCLLCPV QAYCQAFAEG VAEELPVKMK KTAVKQVPLA
VAVLADDEGR VLIRKRDSTG LLANLWEFPS CETDGADGKE KLEQMVGEQY GLQVELTEPI
VSFEHAFSHL VWQLTVFPGR LVHGGPVEEP YRLAPEDELK AYAFPVSHQR VWREYKEWAS
GVRRPD
