4skn
From Proteopedia
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|PDB= 4skn |SIZE=350|CAPTION= <scene name='initialview01'>4skn</scene>, resolution 2.9Å | |PDB= 4skn |SIZE=350|CAPTION= <scene name='initialview01'>4skn</scene>, resolution 2.9Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=URA:URACIL'>URA</scene> | + | |LIGAND= <scene name='pdbligand=DA:2'-DEOXYADENOSINE-5'-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2'-DEOXYCYTIDINE-5'-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5'-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=ORP:2-DEOXY-5-PHOSPHONO-RIBOSE'>ORP</scene>, <scene name='pdbligand=URA:URACIL'>URA</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Uridine_nucleosidase Uridine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.3 3.2.2.3] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Uridine_nucleosidase Uridine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.3 3.2.2.3] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4skn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4skn OCA], [http://www.ebi.ac.uk/pdbsum/4skn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=4skn RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Any uracil bases in DNA, a result of either misincorporation or deamination of cytosine, are removed by uracil-DNA glycosylase (UDG), one of the most efficient and specific of the base-excision DNA-repair enzymes. Crystal structures of human and viral UDGs complexed with free uracil have indicated that the enzyme binds an extrahelical uracil. Such binding of undamaged extrahelical bases has been seen in the structures of two bacterial methyltransferases and bacteriophage T4 endonuclease V. Here we characterize the DNA binding and kinetics of several engineered human UDG mutants and present the crystal structure of one of these, which to our knowledge represents the first structure of any eukaryotic DNA repair enzyme in complex with its damaged, target DNA. Electrostatic orientation along the UDG active site, insertion of an amino acid (residue 272) into the DNA through the minor groove, and compression of the DNA backbone flanking the uracil all result in the flipping-out of the damaged base from the DNA major groove, allowing specific recognition of its phosphate, deoxyribose and uracil moieties. Our structure thus provides a view of a productive complex specific for cleavage of uracil from DNA and also reveals the basis for the enzyme-assisted nucleotide flipping by this critical DNA-repair enzyme. | Any uracil bases in DNA, a result of either misincorporation or deamination of cytosine, are removed by uracil-DNA glycosylase (UDG), one of the most efficient and specific of the base-excision DNA-repair enzymes. Crystal structures of human and viral UDGs complexed with free uracil have indicated that the enzyme binds an extrahelical uracil. Such binding of undamaged extrahelical bases has been seen in the structures of two bacterial methyltransferases and bacteriophage T4 endonuclease V. Here we characterize the DNA binding and kinetics of several engineered human UDG mutants and present the crystal structure of one of these, which to our knowledge represents the first structure of any eukaryotic DNA repair enzyme in complex with its damaged, target DNA. Electrostatic orientation along the UDG active site, insertion of an amino acid (residue 272) into the DNA through the minor groove, and compression of the DNA backbone flanking the uracil all result in the flipping-out of the damaged base from the DNA major groove, allowing specific recognition of its phosphate, deoxyribose and uracil moieties. Our structure thus provides a view of a productive complex specific for cleavage of uracil from DNA and also reveals the basis for the enzyme-assisted nucleotide flipping by this critical DNA-repair enzyme. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Immunodeficiency with hyper IgM, type 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191525 191525]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Slupphaug, G.]] | [[Category: Slupphaug, G.]] | ||
[[Category: Tainer, J A.]] | [[Category: Tainer, J A.]] | ||
| - | [[Category: URA]] | ||
[[Category: dna]] | [[Category: dna]] | ||
[[Category: dna base excision repair]] | [[Category: dna base excision repair]] | ||
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[[Category: uracil]] | [[Category: uracil]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:40:10 2008'' |
Revision as of 02:40, 31 March 2008
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| , resolution 2.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , , | ||||||
| Activity: | Uridine nucleosidase, with EC number 3.2.2.3 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
A NUCLEOTIDE-FLIPPING MECHANISM FROM THE STRUCTURE OF HUMAN URACIL-DNA GLYCOSYLASE BOUND TO DNA
Overview
Any uracil bases in DNA, a result of either misincorporation or deamination of cytosine, are removed by uracil-DNA glycosylase (UDG), one of the most efficient and specific of the base-excision DNA-repair enzymes. Crystal structures of human and viral UDGs complexed with free uracil have indicated that the enzyme binds an extrahelical uracil. Such binding of undamaged extrahelical bases has been seen in the structures of two bacterial methyltransferases and bacteriophage T4 endonuclease V. Here we characterize the DNA binding and kinetics of several engineered human UDG mutants and present the crystal structure of one of these, which to our knowledge represents the first structure of any eukaryotic DNA repair enzyme in complex with its damaged, target DNA. Electrostatic orientation along the UDG active site, insertion of an amino acid (residue 272) into the DNA through the minor groove, and compression of the DNA backbone flanking the uracil all result in the flipping-out of the damaged base from the DNA major groove, allowing specific recognition of its phosphate, deoxyribose and uracil moieties. Our structure thus provides a view of a productive complex specific for cleavage of uracil from DNA and also reveals the basis for the enzyme-assisted nucleotide flipping by this critical DNA-repair enzyme.
About this Structure
4SKN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA., Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA, Nature. 1996 Nov 7;384(6604):87-92. PMID:8900285
Page seeded by OCA on Mon Mar 31 05:40:10 2008
