This title appears in the Scientific Report :
2018
Please use the identifier:
http://hdl.handle.net/2128/17605 in citations.
Please use the identifier: http://dx.doi.org/10.1016/j.str.2017.11.008 in citations.
Second-Shell Basic Residues Expand the Two-Metal-Ion Architecture of DNA and RNA Processing Enzymes
Second-Shell Basic Residues Expand the Two-Metal-Ion Architecture of DNA and RNA Processing Enzymes
Synthesis and scission of phosphodiester bonds in DNA and RNA regulate vital processes within the cell. Enzymes that catalyze these reactions operate mostly via the recognized two-metal-ion mechanism. Our analysis reveals that basic amino acids and monovalent cations occupy structurally conserved po...
Saved in:
Personal Name(s): | Genna, Vito |
---|---|
Colombo, Matteo / De Vivo, Marco (Corresponding author) / Marcia, Marco (Corresponding author) | |
Contributing Institute: |
Computational Biomedicine; INM-9 Computational Biomedicine; IAS-5 |
Published in: | Structure, 26 (2018) S. 40-50 |
Imprint: |
London [u.a.]
Elsevier Science
2018
|
PubMed ID: |
29225080 |
DOI: |
10.1016/j.str.2017.11.008 |
Document Type: |
Journal Article |
Research Program: |
Theory, modelling and simulation |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1016/j.str.2017.11.008 in citations.
Synthesis and scission of phosphodiester bonds in DNA and RNA regulate vital processes within the cell. Enzymes that catalyze these reactions operate mostly via the recognized two-metal-ion mechanism. Our analysis reveals that basic amino acids and monovalent cations occupy structurally conserved positions nearby the active site of many two-metal-ion enzymes for which high-resolution (<3 Å) structures are known, including DNA and RNA polymerases, nucleases such as Cas9, and splicing ribozymes. Integrating multiple-sequence and structural alignments with molecular dynamics simulations, electrostatic potential maps, and mutational data, we found that these elements always interact with the substrates, suggesting that they may play an active role for catalysis, in addition to their electrostatic contribution. We discuss possible mechanistic implications of this expanded two-metal-ion architecture, including inferences on medium-resolution cryoelectron microscopy structures. Ultimately, our analysis may inspire future experiments and strategies for enzyme engineering or drug design to modulate nucleic acid processing. |