4KG4

Crystal structure of Saccharomyces cerevisiae Dcp2 Nudix domain (E198Q mutation)

Summary for 4KG4

• Entry DOI: 10.2210/pdb4kg4/pdb
• Related: 4K6E 4KG3
• Descriptor: mRNA-decapping enzyme subunit 2 (2 entities in total)
• Functional Keywords: nudix, mrna decay, mrna decapping, hydrolase
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Cytoplasm, P-body : P53550
• Total number of polymer chains: 2
• Total formula weight: 34755.85

Authors

Aglietti, R.A.,Floor, S.N.,Gross, J.D. (deposition date: 2013-04-28, release date: 2013-08-21, Last modification date: 2024-02-28)

Primary citation

Aglietti, R.A.,Floor, S.N.,McClendon, C.L.,Jacobson, M.P.,Gross, J.D.
Active site conformational dynamics are coupled to catalysis in the mRNA decapping enzyme dcp2.
Structure, 21:1571-1580, 2013

PubMed Abstract: Removal of the 5' cap structure by Dcp2 is a major step in several 5'-3' mRNA decay pathways. The activity of Dcp2 is enhanced by Dcp1 and bound coactivators, yet the details of how these interactions are linked to chemistry are poorly understood. Here, we report three crystal structures of the catalytic Nudix hydrolase domain of Dcp2 that demonstrate binding of a catalytically essential metal ion, and enzyme kinetics are used to identify several key active site residues involved in acid/base chemistry of decapping. Using nuclear magnetic resonance and molecular dynamics, we find that a conserved metal binding loop on the catalytic domain undergoes conformational changes during the catalytic cycle. These findings describe key events during the chemical step of decapping, suggest local active site conformational changes are important for activity, and provide a framework to explain stimulation of catalysis by the regulatory domain of Dcp2 and associated coactivators.

PubMed: 23911090
DOI: 10.1016/j.str.2013.06.021

Experimental method

X-RAY DIFFRACTION (1.8 Å)