Structural Basis of Substrate Specificity in Geobacter metallireducens SMUG1.

Abstract:

:Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are critical to maintain genome integrity, in which the base excision repair pathway plays an essential role. In the BER pathway, the uracil DNA glycosylase superfamily is responsible for removing the deaminated bases from DNA and generates apurinic/apyrimidinic (AP) sites. Geobacter metallireducens SMUG1 (GmeSMUG1) is an interesting family 3 enzyme in the UDG superfamily, with dual substrate specificities for DNA with uracil or xanthine. In contrast, the mutant G63P of GmeSMUG1 has exclusive activity for uracil, while N58D is inactive for both substrates, as we have reported previously. However, the structural bases for these substrate specificities are not well understood. In this study, we solved a series of crystal structures of WT and mutants of GmeSMUG1 at relatively high resolutions. These structures provide insight on the molecular mechanism of xanthine recognition for GmeSMUG1 and indicate that H210 plays a key role in xanthine recognition, which is in good agreement with the results of our EMSA and activity assays. More importantly, our mutant structures allow us to build models to rationalize our previous experimental observations of altered substrate activities of these mutants.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Zhang Z,Shen J,Yang Y,Li J,Cao W,Xie W

doi

10.1021/acschembio.6b00164

subject

Has Abstract

pub_date

2016-06-17 00:00:00

pages

1729-36

issue

6

eissn

1554-8929

issn

1554-8937

journal_volume

11

pub_type

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