Structural highlights
Function
NUD18_HUMAN Mediates the hydrolyzis of oxidized nucleoside diphosphate derivatives. Hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. Hydrolyzes 8-oxo-dGDP and 8-oxo-GDP with the same efficiencies. Hydrolyzes also 8-OH-dADP and 2-OH-dADP. Exhibited no or minimal hydrolyzis activity against 8-oxo-dGTP, 8-oxo-GTP, dGTP, GTP, dGDP and GDP. Probably removes oxidized guanine nucleotides from both the DNA and RNA precursor pools.
Publication Abstract from PubMed
Protein stability is often a limiting factor in the development of commercial proteins and biopharmaceuticals, as well as for biochemical and structural studies. Unfortunately, identifying stabilizing mutations is not trivial since most are neutral or deleterious. Here we describe a high-throughput colony-based stability screen, which is a direct and biophysical read-out of intrinsic protein stability in contrast to traditional indirect activity-based methods. By combining the method with a random mutagenesis procedure, we successfully identify thermostable variants from 10 diverse and challenging proteins, including several biotechnologically important proteins such as a single-chain antibody, a commercial enzyme and an FDA-approved protein drug. We also show that thermostabilization of a protein drug using our approach translates into dramatic improvements in long-term stability. As the method is generic and activity independent, it can easily be applied to a wide range of proteins.
Engineering protein thermostability using a generic activity-independent biophysical screen inside the cell.,Asial I, Cheng YX, Engman H, Dollhopf M, Wu B, Nordlund P, Cornvik T Nat Commun. 2013 Dec 19;4:2901. doi: 10.1038/ncomms3901. PMID:24352381[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Asial I, Cheng YX, Engman H, Dollhopf M, Wu B, Nordlund P, Cornvik T. Engineering protein thermostability using a generic activity-independent biophysical screen inside the cell. Nat Commun. 2013 Dec 19;4:2901. doi: 10.1038/ncomms3901. PMID:24352381 doi:http://dx.doi.org/10.1038/ncomms3901
