1emj

URACIL-DNA GLYCOSYLASE BOUND TO DNA CONTAINING A 4'-THIO-2'DEOXYURIDINE ANALOG PRODUCTURACIL-DNA GLYCOSYLASE BOUND TO DNA CONTAINING A 4'-THIO-2'DEOXYURIDINE ANALOG PRODUCT

Structural highlights 1emj is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NonStd Res: Related: 1emh, 1ssp, 2ssp, 4skn, 1akz Activity: Uridine nucleosidase, with EC number 3.2.2.3 Resources: FirstGlance, OCA, RCSB, PDBsum Disease [UNG_HUMAN] Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 (HIGM5) [MIM:608106]. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections. Function [UNG_HUMAN] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Enzymatic transformations of macromolecular substrates such as DNA repair enzyme/DNA transformations are commonly interpreted primarily by active-site functional-group chemistry that ignores their extensive interfaces. Yet human uracil-DNA glycosylase (UDG), an archetypical enzyme that initiates DNA base-excision repair, efficiently excises the damaged base uracil resulting from cytosine deamination even when active-site functional groups are deleted by mutagenesis. The 1.8-A resolution substrate analogue and 2.0-A resolution cleaved product cocrystal structures of UDG bound to double-stranded DNA suggest enzyme-DNA substrate-binding energy from the macromolecular interface is funneled into catalytic power at the active site. The architecturally stabilized closing of UDG enforces distortions of the uracil and deoxyribose in the flipped-out nucleotide substrate that are relieved by glycosylic bond cleavage in the product complex. This experimentally defined substrate stereochemistry implies the enzyme alters the orientation of three orthogonal electron orbitals to favor electron transpositions for glycosylic bond cleavage. By revealing the coupling of this anomeric effect to a delocalization of the glycosylic bond electrons into the uracil aromatic system, this structurally implicated mechanism resolves apparent paradoxes concerning the transpositions of electrons among orthogonal orbitals and the retention of catalytic efficiency despite mutational removal of active-site functional groups. These UDG/DNA structures and their implied dissociative excision chemistry suggest biology favors a chemistry for base-excision repair initiation that optimizes pathway coordination by product binding to avoid the release of cytotoxic and mutagenic intermediates. Similar excision chemistry may apply to other biological reaction pathways requiring the coordination of complex multistep chemical transformations. Uracil-DNA glycosylase-DNA substrate and product structures: conformational strain promotes catalytic efficiency by coupled stereoelectronic effects.,Parikh SS, Walcher G, Jones GD, Slupphaug G, Krokan HE, Blackburn GM, Tainer JA Proc Natl Acad Sci U S A. 2000 May 9;97(10):5083-8. PMID:10805771 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA glycosylase Uracil-DNA glycosylase

spinqualitylabelsall models 1emj, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image