Solution Structure of RCL, a Novel 2′-Deoxyribonucleoside 5′-Monophosphate N-glycosidase

Kiran Doddapaneni, Bryon Mahler, Ryan Pavlovicz, Adam Haushalter, Chunhua Yuan, Zhengrong Wu

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

RCL is an enzyme that catalyzes the N-glycosidic bond cleavage of purine 2′-deoxyribonucleoside 5′-monophosphates, a novel enzymatic reaction reported only recently. In this work, we determined the solution structure by multidimensional NMR and provide a structural framework to elucidate its mechanism with computational simulation. RCL is a symmetric homodimer, with each monomer consisting of a five-stranded parallel β-sheet sandwiched between five α-helices. Three of the helices form the dimer interface, allowing two monomers to pack side by side. The overall architecture featuring a Rossmann fold is topologically similar to that of deoxyribosyltransferases, with major differences observed in the putative substrate binding pocket and the C-terminal tail. The latter is seemingly flexible and projecting away from the core structure in RCL, but loops back and is positioned at the bottom of the neighboring active site in the transferases. This difference may bear functional implications in the context of nucleobase recognition involving the C-terminal carboxyl group, which is only required in the reverse reaction by the transferases. It was also noticed that residues around the putative active site show significant conformational variation, suggesting that protein dynamics may play an important role in the enzymatic function of apo-RCL. Overall, the work provides invaluable insight into the mechanism of a novel N-glycosidase from the structural point of view, which in turn will allow rational anti-tumor and anti-angiogenesis drug design.

Original languageEnglish (US)
Pages (from-to)423-434
Number of pages12
JournalJournal of Molecular Biology
Volume394
Issue number3
DOIs
StatePublished - Dec 4 2009
Externally publishedYes

Keywords

  • N-glycosidase
  • RCL

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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