Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hetero-hexameric protein system is developed in this study, which not only functions as cross-linkers for hydrogel formation but also offers docking sites for controlled delivery of bioactive molecules. First, a hexameric protein with two, four, and six tax-interacting protein-1 (TIP-1), respectively (named as 2T, 4T, and 6T), is designed and obtained. As the hexapeptide ligand (WRESAI) can specifically bind to TIP-1 with high affinity, the hexameric proteins of 2T, 4T, and 6T can be used to crosslink the self-assembling nanofibers of Nap-GFFYGGGWRESAI, leading to formation of injectable biohybrid hydrogels with tunable mechanical properties. Furthermore, a hetero-hexameric protein containing four TIP-1 and two C-terminal moiety of the pneumococcal cell-wall amidase LytA (C-LytA) proteins is designed and engineered (named as 4T2C). The 4T2C proteins can not only serve as cross-linkers for hydrogel formation but also provide docking sites for loading and controlled release of model drug Rhoda-GGK'. This study opens up new opportunities for further development of multifunctional hetero- recombinant protein-based hydrogels for biological applications.
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PMID:Rational design of multifunctional hetero-hexameric proteins for hydrogel formation and controlled delivery of bioactive molecules. 2486

Although CRISPR/Cas9 technology has created a renaissance in genome engineering, particularly for gene knockout generation, methods to introduce precise single base changes are also highly desirable. The covalent fusion of a DNA-editing enzyme such as APOBEC to a Cas9 nickase complex has heightened hopes for such precision genome engineering. However, current cytosine base editors are prone to undesirable off-target mutations, including, most frequently, target-adjacent mutations. Here, we report a method to "attract" the DNA deaminase, APOBEC3B, to a target cytosine base for specific editing with minimal damage to adjacent cytosine bases. The key to this system is fusing an APOBEC-interacting protein (not APOBEC itself) to Cas9n, which attracts nuclear APOBEC3B transiently to the target site for editing. Several APOBEC3B interactors were tested and one, hnRNPUL1, demonstrated proof-of-concept with successful C-to-T editing of episomal and chromosomal substrates and lower frequencies of target-adjacent events.
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PMID:MagnEdit-interacting factors that recruit DNA-editing enzymes to single base targets. 3209 50