3-methyladenine-DNA glycosylase II: the crystal structure of an AlkA-hypoxanthine complex suggests the possibility of product inhibition.
Escherichia coli (E. coli) protein 3-methyladenine-DNA glycosylase II (AlkA) functions primarily by removing alkylation damage from duplex and single stranded DNA. A crystal structure of AlkA was refined to 2.0 A resolution. This structure in turn was used to refine an AlkA-hypoxanthine (substrate) complex structure to 2.4 A resolution. The complex structure shows hypoxanthine located in AlkA's active site stacked between residues W218 and Y239. The structural analysis of the AlkA and AlkA-hypoxanthine structures indicate that free hypoxanthine binding in the active site may inhibit glycosylase activity.
Teale
Michael
M
Laboratory for Structural Biology, University of Alabama in Huntsville, 35899, USA. tealem@email.uah.edu
Symersky
Jindrich
J
DeLucas
Larry
L
D003460:Crystallization; D045647:DNA Glycosylases; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D007042:Hypoxanthines / Q000737:chemistry*; D008958:Models, Molecular; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry; D014961:X-Ray Diffraction
D004791:Enzyme Inhibitors; D007042:Hypoxanthines; D014443:Tyrosine; D014364:Tryptophan; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C076131:DNA-3-methyladenine glycosidase II