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UniProtKB:Accession Number | P13051 | P12295 | P10186 |
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Entry name | UNG_HUMAN | UNG_ECOLI | UNG_HHV11 |
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Activity |
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Subunit | Monomer. Interacts with HIV-1 Vpr. | Monomer. |
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Subcellular location | Isoform 1: Mitochondrion.,Isoform 2: Nucleus. | Cytoplasm. |
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Cofactor |
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Compound table: links to PDB-related databases & PoSSuM |
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| Substrates | Products |
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KEGG-id | L00033 | C00001 | C00106 | C02270 |
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Compound | DNA uracil | H2O | Uracil | Base-removed DNA |
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Type | amide group,nucleic acids | H2O | amide group,aromatic ring (with nitrogen atoms) | carbohydrate,nucleic acids,phosphate group/phosphate ion |
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ChEBI |
| 15377
| 17568
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PubChem |
| 22247451 962
| 1174
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| | | | | | | | | | | |
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1emhA |  |  |  |  |  |  |  | Analogue:T-G-T-P2U-A-T-C-T-T(chain B:double stranded DNA) | | Unbound | Unbound |
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1emjA |  |  |  |  |  |  |  | Unbound | | Bound:URA | Bound:T-G-T-ASU-A-T-C-T-T(chain B:double stranded DNA) |
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1eugA |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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1flzA |  |  |  |  |  |  |  | Unbound | | Bound:URA | Unbound |
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1sspE |  |  |  |  |  |  |  | Unbound | | Bound:URA | Bound:C-T-G-T-ORP-A-T-C-T-T(chain A:double stranded DNA) |
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1ughE |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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1uugA |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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1uugC |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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2eugA |  |  |  |  |  |  |  | Unbound | | Bound:URA | Unbound |
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2sspE |  |  |  |  |  |  |  | Unbound | | Unbound | Bound:C-T-G-T-AAB-A-T-C-T-T(chain A:double stranded DNA) |
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2uugA |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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2uugB |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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3eugA |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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4eugA |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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4sknE |  |  |  |  |  |  |  | Unbound | | Bound:URA | Bound:T-G-G-G-ORP-G-G-C-T-T(chain A:double stranded DNA) |
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5eugA |  |  |  |  |  |  |  | Unbound | | Bound:URA | Unbound |
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1lauE |  |  |  |  |  |  |  | Analogue:T-T-T(chain D:single stranded DNA) | | Unbound | Unbound |
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1udgA |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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1udhA |  |  |  |  |  |  |  | Unbound | | Bound:URA | Unbound |
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References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
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[1] | p.873-875, Fig.5 | 2 | [3] | p.491-493, Fig.5 | 2 | [6] | p.5220-5221 |
| [7] | p.4884-4885 |
| [10] | p.22-23 |
| [12] | Fig.5 |
| [13] | Fig.6, Fig.7 |
| [14] | p.190-194, Fig.5 |
| [15] | p.7718 |
| [16] | p.754 |
| [17] | p.6-9, Fig.5 | 2 | [18] | p.15391 |
| [19] | Scheme 1 |
| [20] | p.1928 |
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references | [1] |
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Comments | X-ray crystallography (2.0 Angstroms) |
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Medline ID | 95211838 |
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PubMed ID | 7697717 |
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Journal | Cell |
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Year | 1995 |
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Volume | 80 |
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Pages | 869-78 |
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Authors | Mol CD, Arvai AS, Slupphaug G, Kavli B, Alseth I, Krokan HE, Tainer JA |
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Title | Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis. |
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Related UniProtKB | P13051 |
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[2] |
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Comments | X-ray crystallography (1.9 Angstroms) |
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Medline ID | 95401260 |
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PubMed ID | 7671300 |
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Journal | Cell |
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Year | 1995 |
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Volume | 82 |
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Pages | 701-8 |
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Authors | Mol CD, Arvai AS, Sanderson RJ, Slupphaug G, Kavli B, Krokan HE, Mosbaugh DW, Tainer JA |
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Title | Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: protein mimicry of DNA. |
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Related PDB | 1ugh |
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Related UniProtKB | P13051 |
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[3] |
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PubMed ID | 7845459 |
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Journal | Nature |
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Year | 1995 |
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Volume | 373 |
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Pages | 487-93 |
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Authors | Savva R, McAuley-Hecht K, Brown T, Pearl L |
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Title | The structural basis of specific base-excision repair by uracil-DNA glycosylase. |
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Related PDB | 1lau,1udg,1udh |
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[4] |
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Comments | X-ray crystallography |
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Medline ID | 97055940 |
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PubMed ID | 8900285 |
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Journal | Nature |
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Year | 1996 |
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Volume | 384 |
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Pages | 87-92 |
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Authors | Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA |
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Title | A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. |
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Related PDB | 4skn |
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Related UniProtKB | P13051 |
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[5] |
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Comments | NMR |
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Medline ID | 97407932 |
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PubMed ID | 9261156 |
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Journal | J Biol Chem |
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Year | 1997 |
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Volume | 272 |
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Pages | 21408-19 |
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Authors | Lundquist AJ, Beger RD, Bennett SE, Bolton PH, Mosbaugh DW |
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Title | Site-directed mutagenesis and characterization of uracil-DNA glycosylase inhibitor protein. Role of specific carboxylic amino acids in complex formation with Escherichia coli uracil-DNA glycosylase. |
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Related UniProtKB | P12295 |
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[6] |
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Comments | X-ray crystallography |
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Medline ID | 98393562 |
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PubMed ID | 9724657 |
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Journal | EMBO J |
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Year | 1998 |
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Volume | 17 |
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Pages | 5214-26 |
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Authors | Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA |
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Title | Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. |
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Related PDB | 1ssp,2ssp |
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Related UniProtKB | P13051 |
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[7] |
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Comments | X-ray crystallography |
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Medline ID | 98451580 |
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PubMed ID | 9776748 |
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Journal | Nucleic Acids Res |
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Year | 1998 |
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Volume | 26 |
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Pages | 4880-4887 |
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Authors | Ravishankar R, Bidya Sagar M, Roy S, Purnapatre K, Handa P, Varshney U, Vijayan M |
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Title | X-ray analysis of a complex of Escherichia coli uracil DNA glycosylase (EcUDG) with a proteinaceous inhibitor. The structure elucidation of a prokaryotic UDG. |
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Related PDB | P12295 |
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[8] |
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PubMed ID | 9417045 |
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Journal | J Biol Chem |
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Year | 1998 |
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Volume | 273 |
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Pages | 45-50 |
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Authors | Panayotou G, Brown T, Barlow T, Pearl LH, Savva R |
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Title | Direct measurement of the substrate preference of uracil-DNA glycosylase. |
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[9] |
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Comments | X-ray crystallography |
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Medline ID | 99182421 |
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PubMed ID | 10080896 |
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Journal | J Mol Biol |
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Year | 1999 |
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Volume | 287 |
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Pages | 331-346 |
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Authors | Putnam CD, Shroyer MJ, Lundquist AJ, Mol CD, Arvai AS, Mosbaugh DW, Tainer JA |
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Title | Protein mimicry of DNA from crystal structures of the uracil-DNA glycosylase inhibitor protein and its complex with Escherichia coli uracil-DNA glycosylase. |
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Related PDB | 1uug,2uug |
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Related UniProtKB | P12295 |
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[10] |
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Comments | X-ray crystallography (1.43-1.60 Angstroms) |
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Medline ID | 99188668 |
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PubMed ID | 10090282 |
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Journal | Proteins |
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Year | 1999 |
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Volume | 35 |
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Pages | 13-24 |
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Authors | Xiao G, Tordova M, Jagadeesh J, Drohat AC, Stivers JT, Gilliland GL |
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Title | Crystal structure of Escherichia coli uracil DNA glycosylase and its complexes with uracil and glycerol: structure and glycosylase mechanism revisited. |
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Related PDB | 1eug,2eug,3eug,4eug,5eug |
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Related UniProtKB | P12295 |
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[11] |
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Comments | X-ray crystallography |
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Medline ID | 20480086 |
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PubMed ID | 11027138 |
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Journal | Biochemistry |
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Year | 2000 |
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Volume | 39 |
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Pages | 12585-12594 |
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Authors | Werner RM, Jiang YL, Gordley RG, Jagadeesh GJ, Ladner JE, Xiao G, Tordova M, Gilliland GL, Stivers JT |
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Title | Stressing-out DNA? The contribution of serine-phosphodiester interactions in catalysis by uracil DNA glycosylase. |
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Related PDB | 1flz |
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Related UniProtKB | P12295 |
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[12] |
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Comments | X-ray crystallography (1.8-2.0 Angstroms) |
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PubMed ID | 10805771 |
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Journal | Proc Natl Acad Sci U S A |
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Year | 2000 |
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Volume | 97 |
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Pages | 5083-5088 |
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Authors | Parikh SS, Walcher G, Jones GD, Slupphaug G, Krokan HE, Blackburn GM, Tainer JA |
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Title | Uracil-DNA glycosylase-DNA substrate and product structures: conformational strain promotes catalytic efficiency by coupled stereoelectronic effects. |
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Related PDB | 1emh,1emj |
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[13] |
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PubMed ID | 10946228 |
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Journal | Mutat Res |
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Year | 2000 |
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Volume | 460 |
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Pages | 183-99 |
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Authors | Parikh SS, Putnam CD, Tainer JA |
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Title | Lessons learned from structural results on uracil-DNA glycosylase. |
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[14] |
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PubMed ID | 11087352 |
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Journal | Biochemistry |
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Year | 2000 |
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Volume | 39 |
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Pages | 14054-64 |
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Authors | Werner RM, Stivers JT |
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Title | Kinetic isotope effect studies of the reaction catalyzed by uracil DNA glycosylase: evidence for an oxocarbenium ion-uracil anion intermediate. |
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[15] |
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PubMed ID | 11412125 |
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Journal | Biochemistry |
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Year | 2001 |
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Volume | 40 |
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Pages | 7710-9 |
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Authors | Jiang YL, Stivers JT |
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Title | Reconstructing the substrate for uracil DNA glycosylase: tracking the transmission of binding energy in catalysis. |
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[16] |
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PubMed ID | 11607036 |
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Journal | Nature |
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Year | 2001 |
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Volume | 413 |
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Pages | 752-5 |
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Authors | Dinner AR, Blackburn GM, Karplus M |
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Title | Uracil-DNA glycosylase acts by substrate autocatalysis. |
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[17] |
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PubMed ID | 11716455 |
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Journal | Arch Biochem Biophys |
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Year | 2001 |
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Volume | 396 |
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Pages | 1-9 |
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Authors | Stivers JT, Drohat AC |
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Title | Uracil DNA glycosylase: insights from a master catalyst. |
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[18] |
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PubMed ID | 11859082 |
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Journal | J Biol Chem |
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Year | 2002 |
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Volume | 277 |
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Pages | 15385-92 |
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Authors | Jiang YL, Drohat AC, Ichikawa Y, Stivers JT |
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Title | Probing the limits of electrostatic catalysis by uracil DNA glycosylase using transition state mimicry and mutagenesis. |
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[19] |
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PubMed ID | 12136091 |
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Journal | Nucleic Acids Res |
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Year | 2002 |
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Volume | 30 |
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Pages | 3086-95 |
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Authors | Handa P, Acharya N, Varshney U |
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Title | Effects of mutations at tyrosine 66 and asparagine 123 in the active site pocket of Escherichia coli uracil DNA glycosylase on uracil excision from synthetic DNA oligomers: evidence for the occurrence of long-range interactions between the enzyme and substrate. |
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[20] |
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PubMed ID | 12590578 |
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Journal | Biochemistry |
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Year | 2003 |
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Volume | 42 |
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Pages | 1922-9 |
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Authors | Jiang YL, Ichikawa Y, Song F, Stivers JT |
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Title | Powering DNA repair through substrate electrostatic interactions. |
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comments | Many catalytic mechanisms of this enzyme, UDG, have been proposed to date. This enzyme exists ubiquitously, and its active sites are conserved throughout those from viral, eukaryotic, and mammalian sources [7]. Initially, the catalysis of UDG was considered to be SN2-like reaction mechanism, in which Asp88 and His210 (of 1lau; UDG from herpes simplex virus type-1) acts as base and acid, respectively [1], [3] & [7]. In recent years, however, an alternative mechanism, SN1-like dissociative mechanism, in which oxocarbenium-ion transition-state would be stablised, was proposed [10], [13]. The catalysis is supported by the following factors; (a) the active site residues (see [17], [18], [19]) (b) the DNA backbone phosphodiester (especially, from +1, -1, & -2 subsite nucleotides) (see [11], [15], [16], [17]) (c) the normally trigonal planar 1-position of uracil strained to an almost tetrahedral geometry (see [12], [14], [17], [20]) Taken together, the reaction proceeds as follows: (1) An oxocarbenium-ion transition-state is formed (SN1-like dissociative mechanism), where negative charge and positive charge are developed on uracil group and O4' (or C1') atom of deoxyribose, respectively. Here, Asp88 and His210 stabilize the negative charge and positive charge, respectively. Moreover, the stabilization of the positive charge must be assisted by nearby DNA backbone phosphodiester groups. (2) Asp88 acts as a general base to activate a water. (3) The activated water makes a nucleophilic attack on the C1' atom. (4) His210 acts as a general acid to protonate the N1 atom of the leaving uracil.
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created | updated |
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2002-09-27 | 2009-02-26 |
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