Details

Autor(en) / Beteiligte

• Mol, Clifford D
• Arvai, Andrew S
• Slupphaug, Geir
• Kavli, Bodil
• Alseth, Ingrun
• Krokan, Hans E
• Tainer, John A

Titel

Crystal structure and mutational analysis of human uracil-DNA glycosylase: Structural basis for specificity and catalysis

Ist Teil von

• Cell, 1995-03, Vol.80 (6), p.869-878

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1995

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Crystal structures of the DNA repair enzyme human uracil-DNA glycosylase (UDG), combined with mutational analysis, reveal the structural basis for the specificity of the enzyme. Within the classic α/β fold of UDG, sequence-conserved residues form a positively charged, active-site groove the width of duplex DNA, at the C-terminal edge of the central four-stranded parallel β sheet. In the UDG-6-aminouracil complex, uracil binds at the base of the groove within a rigid preformed pocket that confers selectivity for uracil over other bases by shape complementarity and by main chain and Asn-204 side chain hydrogen bonds. Main chain nitrogen atoms are positioned to stabilize the oxyanion intermediate generated by His-268 acting via nucleophilic attack or general base mechanisms. Specific binding of uracil flipped out from a DNA duplex provides a structural mechanism for damaged base recognition.