Efficacy of a tip of the big toe remodeling in the distal nail embedding with bone overgrowth of the distal phalanx.

INTRODUCTION: Distal nail embedding due to hyponychium hypertrophy can be caused by traumatic or surgical avulsion of the nail. As a consequence of these changes, the nail plate is blocked through the deformed tip of the toe. Changes that occur at the tip of the big toe are due to bone growth on the dorsal surface of the distal end of the distal phalanx. This study aimed to present a surgical technique for the treatment of hypertrophy of the tip of the toe and evaluate its effectiveness. MATERIAL AND METHODS: The surgical technique involved remodeling of the tip of the big toe, with removal of the hypertrophied bone of the distal phalanx. The procedure was assessed by using a questionnaire. RESULTS: We included the 108 distal embedded nails. A total of 85% of respondents were satisfied with the procedure. Nearly 80% of patients rated the cosmetic effect as good or very good. CONCLUSIONS: The technique was an effective treatment and increased the quality of life of those with disorders of nail growth associated with hypertrophy of the tip and hyponychium, with bone overgrowth.

Functional and structural characterization of IdnL7, an adenylation enzyme involved in incednine biosynthesis.

Adenylation enzymes play an important role in the selective incorporation of the cognate carboxylate substrates in natural product biosynthesis. Here, the biochemical and structural characterization of the adenylation enzyme IdnL7, which is involved in the biosynthesis of the macrolactam polyketide antibiotic incednine, is reported. Biochemical analysis showed that IdnL7 selects and activates several small amino acids. The structure of IdnL7 in complex with an L-alanyl-adenylate intermediate mimic, 5'-O-[N-(L-alanyl)sulfamoyl]adenosine, was determined at 2.1 Šresolution. The structure of IdnL7 explains the broad substrate specificity of IdnL7 towards small L-amino acids.

Biochemical characterization and structural insight into aliphatic ß-amino acid adenylation enzymes IdnL1 and CmiS6.

Macrolactam antibiotics such as incednine and cremimycin possess an aliphatic ß-amino acid as a starter unit of their polyketide chain. In the biosynthesis of incednine and cremimycin, unique stand-alone adenylation enzymes IdnL1 and CmiS6 select and activate the proper aliphatic ß-amino acid as a starter unit. In this study, we describe the enzymatic characterization and the structural basis of substrate specificity of IdnL1 and CmiS6. Functional analysis revealed that IdnL1 and CmiS6 recognize 3-aminobutanoic acid and 3-aminononanoic acid, respectively. We solved the X-ray crystal structures of IdnL1 and CmiS6 to understand the recognition mechanism of these aliphatic ß-amino acids. These structures revealed that IdnL1 and CmiS6 share a common recognition motif that interacts with the ß-amino group of the substrates. However, the hydrophobic side-chains of the substrates are accommodated differently in the two enzymes. IdnL1 has a bulky Leu220 located close to the terminal methyl group of 3-aminobutanoate of the trapped acyl-adenylate intermediate to construct a shallow substrate-binding pocket. In contrast, CmiS6 possesses Gly220 at the corresponding position to accommodate 3-aminononanoic acid. This structural observation was supported by a mutational study. Thus, the size of amino acid residue at the 220 position is critical for the selection of an aliphatic ß-amino acid substrate in these adenylation enzymes. Proteins 2017; 85:1238-1247. © 2017 Wiley Periodicals, Inc.

The crystal structure of the adenylation enzyme VinN reveals a unique ß-amino acid recognition mechanism.

Adenylation enzymes play important roles in the biosynthesis and degradation of primary and secondary metabolites. Mechanistic insights into the recognition of α-amino acid substrates have been obtained for α-amino acid adenylation enzymes. The Asp residue is invariant and is essential for the stabilization of the α-amino group of the substrate. In contrast, the ß-amino acid recognition mechanism of adenylation enzymes is still unclear despite the importance of ß-amino acid activation for the biosynthesis of various natural products. Herein, we report the crystal structure of the stand-alone adenylation enzyme VinN, which specifically activates (2S,3S)-3-methylaspartate (3-MeAsp) in vicenistatin biosynthesis. VinN has an overall structure similar to that of other adenylation enzymes. The structure of the complex with 3-MeAsp revealed that a conserved Asp(230) residue is used in the recognition of the ß-amino group of 3-MeAsp similar to α-amino acid adenylation enzymes. A mutational analysis and structural comparison with α-amino acid adenylation enzymes showed that the substrate-binding pocket of VinN has a unique architecture to accommodate 3-MeAsp as a ß-amino acid substrate. Thus, the VinN structure allows the first visualization of the interaction of an adenylation enzyme with a ß-amino acid and provides new mechanistic insights into the selective recognition of ß-amino acids in this family of enzymes.