UDG

Uracil DNA glycosylase superfamily

• SMART accession number: SM00986
• Interpro abstract (IPR005122):

  This entry represents various uracil-DNA glycosylases and related DNA glycosylases (EC 3.2.2), such as uracil-DNA glycosylase [(PUBMED:7697717)], thermophilic uracil-DNA glycosylase [(PUBMED:10339434)], G:T/U mismatch-specific DNA glycosylase (Mug) [(PUBMED:9489705)], and single-strand selective monofunctional uracil-DNA glycosylase (SMUG1) [(PUBMED:2820976)]. These proteins have a 3-layer alpha/beta/alpha structure. Uracil-DNA glycosylases are DNA repair enzymes that excise uracil residues from DNA by cleaving the N-glycosylic bond, initiating the base excision repair pathway. Uracil in DNA can arise either through the deamination of cytosine to form mutagenic U:G mispairs, or through the incorporation of dUMP by DNA polymerase to form U:A pairs [(PUBMED:17116429)]. These aberrant uracil residues are genotoxic [(PUBMED:16860315)]. The sequence of uracil-DNA glycosylase is extremely well conserved [(PUBMED:2555154)] in bacteria and eukaryotes as well as in herpes viruses. More distantly related uracil-DNA glycosylases are also found in poxviruses [(PUBMED:8389453)]. In eukaryotic cells, UNG activity is found in both the nucleus and the mitochondria. Human UNG1 protein is transported to both the mitochondria and the nucleus [(PUBMED:8332455)]. The N-terminal 77 amino acids of UNG1 seem to be required for mitochondrial localization, but the presence of a mitochondrial transit peptide has not been directly demonstrated. The most N-terminal conserved region contains an aspartic acid residue which has been proposed, based on X-ray structures [(PUBMED:7845459)] to act as a general base in the catalytic mechanism.

There are 3648 UDG domains in 3648 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: chromatin

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Aravind L, Koonin EV
• The alpha/beta fold uracil DNA glycosylases: a common origin with diversefates.
• Genome Biol. 2000; 1: 7-7

BACKGROUND: Uracil DNA glycosylases (UDGs) are major repair enzymes thatprotect DNA from mutational damage caused by uracil incorporated as aresult of a polymerase error or deamination of cytosine. Four distinctfamilies of UDGs have been identified, which show very limited sequencesimilarity to each other, although two of them have been shown to possessthe same structural fold. The structural and evolutionary relationshipsbetween the rest of the UDGs remain uncertain. RESULTS: Using sequenceprofile searches, multiple alignment analysis and protein structurecomparisons, we show here that all known UDGs possess the same fold andmust have evolved from a common ancestor. Although all UDGs catalyzeessentially the same reaction, significant changes in the configuration ofthe catalytic residues were detected within their common fold, whichprobably results in differences in the biochemistry of these enzymes. Theextreme sequence divergence of the UDGs, which is unusual for enzymes withthe same principal activity, is probably due to the major role of theuracil-flipping caused by the conformational strain enacted by the enzymeon uracil-containing DNA, as compared with the catalytic action ofindividual polar residues. We predict two previously undetected familiesof UDGs and delineate a hypothetical scenario for their evolution.CONCLUSIONS: UDGs form a single protein superfamily with a distinctstructural fold and a common evolutionary origin. Differences in thecatalytic mechanism of the different families combined with theconstruction of the catalytic pocket have, however, resulted in extremesequence divergence of these enzymes.

• Barrett TE et al.
• Crystal structure of a G:T/U mismatch-specific DNA glycosylase: mismatchrecognition by complementary-strand interactions.
• Cell. 1998; 92: 117-29

G:U mismatches resulting from deamination of cytosine are the most commonpromutagenic lesions occurring in DNA. Uracil is removed in abase-excision repair pathway by uracil DNA-glycosylase (UDG), whichexcises uracil from both single- and double-stranded DNA. Recently, abiochemically distinct family of DNA repair enzymes has been identified,which excises both uracil and thymine, but only from mispairs withguanine. Crystal structures of the mismatch-specific uracilDNA-glycosylase (MUG) from E. coli, and of a DNA complex, reveal aremarkable structural and functional homology to UDGs despite low sequenceidentity. Details of the MUG structure explain its thymine DNA-glycosylaseactivity and the specificity for G:U/T mispairs, which derives from directrecognition of guanine on the complementary strand.

Structure (3D structures containing this domain)

3D Structures of UDG domains in PDB

PDB code	Title
1akz	Human uracil-dna glycosylase
1emh	Crystal structure of human uracil-dna glycosylase bound to uncleaved substrate-containing dna
1emj	Uracil-dna glycosylase bound to dna containing a 4'-thio- 2'deoxyuridine analog product
1eug	Crystal structure of escherichia coli uracil dna glycosylase and its complexes with uracil and glycerol: structure and glycosylase mechanism revisited
1eui	Escherichia coli uracil-dna glycosylase complex with uracil- dna glycosylase inhibitor protein
1flz	Uracil dna glycosylase with uaap
1l9g	Crystal structure of uracil-dna glycosylase from t. maritima
1lau	Uracil-dna glycosylase
1lqg	Escherichia coli uracil-dna glycosylase complex with uracil- dna glycosylase inhibitor protein
1lqj	Escherichia coli uracil-dna glycosylase
1lqm	Escherichia coli uracil-dna glycosylase complex with uracil- dna glycosylase inhibitor protein
1mtl	Non-productive mug-dna complex
1mug	G:t/u mismatch-specific dna glycosylase from e.coli
1mwi	Crystal structure of a mug-dna product complex
1mwj	Crystal structure of a mug-dna pseudo substrate complex
1okb	Crystal structure of uracil-dna glycosylase from atlantic cod (gadus morhua)
1q3f	Uracil dna glycosylase bound to a cationic 1-aza-2'- deoxyribose-contianing dna
1ssp	Wild-type uracil-dna glycosylase bound to uracil-containing dna
1udg	The structural basis of specific base excision repair by uracil-dna glycosylase
1udh	The structural basis of specific base excision repair by uracil-dna glycosylase
1udi	Nucleotide mimicry in the crystal structure of the uracil- dna glycosylase-uracil glycosylase inhibitor protein complex
1ugh	Crystal structure of human uracil-dna glycosylase in complex with a protein inhibitor: protein mimicry of dna
1ui0	Crystal structure of uracil-dna glycosylase from thermus thermophilus hb8
1ui1	Crystal structure of uracil-dna glycosylase from thermus thermophilus hb8
1uug	Escherichia coli uracil-dna glycosylase:inhibitor complex with wild-type udg and wild-type ugi
1vk2	Crystal structure of uracil-dna glycosylase (tm0511) from thermotoga maritima at 1.90 a resolution
1wyw	Crystal structure of sumo1-conjugated thymine dna glycosylase
1yuo	Optimisation of the surface electrostatics as a strategy for cold adaptation of uracil-dna n-glycosylase (ung)from atlantic cod (gadus morhua)
2boo	The crystal structure of uracil-dna n-glycosylase (ung) from deinococcus radiodurans.
2c53	A comparative study of uracil dna glycosylases from human and herpes simplex virus type 1
2c56	A comparative study of uracil dna glycosylases from human and herpes simplex virus type 1
2d07	Crystal structure of sumo-3-modified thymine-dna glycosylase
2d3y	Crystal structure of uracil-dna glycosylase from thermus thermophilus hb8
2ddg	Crystal structure of uracil-dna glycosylase in complex with ap:g containing dna
2dem	Crystal structure of uracil-dna glycosylase in complex with ap:a containing dna
2dp6	Crystal structure of uracil-dna glycosylase in complex with ap:c containing dna
2eug	Crystal structure of escherichia coli uracil dna glycosylase and its complexes with uracil and glycerol: structure and glycosylase mechanism revisited
2hxm	Complex of ung2 and a small molecule synthetic inhibitor
2j8x	Epstein-barr virus uracil-dna glycosylase in complex with ugi from pbs-2
2jhq	Crystal structure of uracil dna-glycosylase from vibrio cholerae
2oxm	Crystal structure of a ung2/modified dna complex that represent a stabilized short-lived extrahelical state in ezymatic dna base flipping
2oyt	Crystal structure of ung2/dna(tm)
2rba	Structure of human thymine dna glycosylase bound to abasic and undamaged dna
2ssp	Leucine-272-alanine uracil-dna glycosylase bound to abasic site-containing dna
2uug	Escherichia coli uracil-dna glycosylase:inhibitor complex with h187d mutant udg and wild-type ugi
2zhx	Crystal structure of uracil-dna glycosylase from mycobacterium tuberculosis in complex with a proteinaceous inhibitor
3cxm	Leishmania naiffi uracil-dna glycosylase in complex with 5- bromouracil
3eug	Crystal structure of escherichia coli uracil dna glycosylase and its complexes with uracil and glycerol: structure and glycosylase mechanism revisited
3fcf	Complex of ung2 and a fragment-based designed inhibitor
3fci	Complex of ung2 and a fragment-based designed inhibitor
3fck	Complex of ung2 and a fragment-based design inhibitor
3fcl	Complex of ung2 and a fragment-based designed inhibitor
3ikb	The structure of a conserved protein from streptococcus mutans ua159.
4eug	Crystallographic and enzymatic studies of an active site variant h187q of escherichia coli uracil dna glycosylase: crystal structures of mutant h187q and its uracil complex
4skn	A nucleotide-flipping mechanism from the structure of human uracil-dna glycosylase bound to dna
5eug	Crystallographic and enzymatic studies of an active site variant h187q of escherichia coli uracil dna glycosylase: crystal structures of mutant h187q and its uracil complex

Links (links to other resources describing this domain)

• PFAM: UDG
• INTERPRO: IPR005122