Structural similarities between SAM and ATP recognition motifs and detection of ATP binding in a SAM binding DNA methyltransferase.

S-adenosylmethionine (SAM) is a ubiquitous co-factor that serves as a donor for methylation reactions and additionally serves as a donor of other functional groups such as amino and ribosyl moieties in a variety of other biochemical reactions. Such versatility in function is enabled by the ability of SAM to be recognized by a wide variety of protein molecules that vary in their sequences and structural folds. To understand what gives rise to specific SAM binding in diverse proteins, we set out to study if there are any structural patterns at their binding sites. A comprehensive analysis of structures of the binding sites of SAM by all-pair comparison and clustering, indicated the presence of 4 different site-types, only one among them being well studied. For each site-type we decipher the common minimum principle involved in SAM recognition by diverse proteins and derive structural motifs that are characteristic of SAM binding. The presence of the structural motifs with precise three-dimensional arrangement of amino acids in SAM sites that appear to have evolved independently, indicates that these are winning arrangements of residues to bring about SAM recognition. Further, we find high similarity between one of the SAM site types and a well known ATP binding site type. We demonstrate using in vitro experiments that a known SAM binding protein, HpyAII.M1, a type 2 methyltransferase can bind and hydrolyse ATP. We find common structural motifs that explain this, further supported through site-directed mutagenesis. Observation of similar motifs for binding two of the most ubiquitous ligands in multiple protein families with diverse sequences and structural folds presents compelling evidence at the molecular level in favour of convergent evolution.

Effect of micro-osteoperforations on the rate of orthodontic tooth movement and expression of biomarkers: a randomized controlled clinical trial.

INTRODUCTION: Micro-osteoperforation is a minimally invasive technique that has been used to accelerate orthodontic tooth movement and reduce treatment duration. However, literature presents conflicting reports about this technique. OBJECTIVE: To evaluate the effectiveness of micro-osteoperforations on the rate of canine retraction and expression of biomarkers in gingival crevicular fluid (GCF). METHODS: This was a randomized clinical trial with split-mouth study design. Thirty adult subjects with age above 18 years (20.32 ± 1.96) who required fixed orthodontic treatment and extraction of maxillary first premolars were enrolled and randomly allocated to either the experimental or control group. Randomization was performed by block randomization method, with a 1:1 allocation ratio. The experimental group received three micro-ostoperforations (MOPs) distal to maxillary canine, using the Lance pilot drill. The retraction of maxillary canine was performed with NiTi coil-spring (150g) in both experimental and control groups. The primary outcome was the evaluation of canine retraction rate, measured on study models from the baseline to 16 weeks of canine retraction. Secondary outcomes were the estimation of alkaline and acid phosphates activity in GCF at 0, 1, 2, 3, and 4 weeks. RESULTS: There was a statistically significant difference in the rate of canine retraction only after the first 4 weeks. Subsequently there was no statistically significant difference from the eighth to the sixteenth weeks between MOPs and control group. There was a statistically significant difference in alkaline and acid phosphates activity in GCF between MOPs and control groups during the initial 4 weeks of canine retraction. CONCLUSION: Micro-ostoperforation increased the rate of tooth movement only for the first 4 weeks; thereafter, no effect was observed on the rate of canine retraction during 8, 12 and 16 weeks. A marked increase in biomarker activity in the first month was observed.

Effect of micro-osteoperforations on the rate of orthodontic tooth movement and expression of biomarkers: a randomized controlled clinical trial

ABSTRACT Introduction: Micro-osteoperforation is a minimally invasive technique that has been used to accelerate orthodontic tooth movement and reduce treatment duration. However, literature presents conflicting reports about this technique. Objective: To evaluate the effectiveness of micro-osteoperforations on the rate of canine retraction and expression of biomarkers in gingival crevicular fluid (GCF). Methods: This was a randomized clinical trial with split-mouth study design. Thirty adult subjects with age above 18 years (20.32 ± 1.96) who required fixed orthodontic treatment and extraction of maxillary first premolars were enrolled and randomly allocated to either the experimental or control group. Randomization was performed by block randomization method, with a 1:1 allocation ratio. The experimental group received three micro-ostoperforations (MOPs) distal to maxillary canine, using the Lance pilot drill. The retraction of maxillary canine was performed with NiTi coil-spring (150g) in both experimental and control groups. The primary outcome was the evaluation of canine retraction rate, measured on study models from the baseline to 16 weeks of canine retraction. Secondary outcomes were the estimation of alkaline and acid phosphates activity in GCF at 0, 1, 2, 3, and 4 weeks. Results: There was a statistically significant difference in the rate of canine retraction only after the first 4 weeks. Subsequently there was no statistically significant difference from the eighth to the sixteenth weeks between MOPs and control group. There was a statistically significant difference in alkaline and acid phosphates activity in GCF between MOPs and control groups during the initial 4 weeks of canine retraction. Conclusion: Micro-ostoperforation increased the rate of tooth movement only for the first 4 weeks; thereafter, no effect was observed on the rate of canine retraction during 8, 12 and 16 weeks. A marked increase in biomarker activity in the first month was observed.

RESUMO Introdução: As micro-osteoperfurações (MOPs) são uma técnica minimamente invasiva que tem sido utilizada para acelerar a movimentação dentária ortodôntica e reduzir o tempo de tratamento. No entanto, existem relatos conflitantes sobre o uso dessa técnica. Objetivo: Avaliar a eficácia das MOPs em acelerar a taxa do movimento de retração de caninos e na expressão de biomarcadores no fluido crevicular gengival (FCG). Métodos: Esse foi um ensaio clínico randomizado com desenho de estudo do tipo boca dividida. Trinta indivíduos adultos com idade acima de 18 anos (20,32 ± 1,96 anos) que necessitavam de tratamento ortodôntico fixo e extração de primeiros pré-molares superiores foram incluídos e aleatoriamente alocados para o grupo experimental ou grupo controle. A randomização foi realizada pelo método de randomização em bloco, com proporção de alocação de 1:1. O grupo experimental recebeu três MOPs distais ao canino superior, utilizando uma broca piloto em formato de lança. A retração do canino superior foi realizada com mola helicoidal de NiTi (150g) nos dois grupos, experimental e controle. O desfecho primário foi a avaliação da taxa de retração dos caninos, medida em modelos de estudo do início da retração até 16 semanas depois. O desfecho secundário foi a estimativa da atividade da fosfatase alcalina e ácida no FCG após 0, 1, 2, 3 e 4 semanas. Resultados: Houve uma diferença estatisticamente significativa na taxa de retração dos caninos somente após as quatro primeiras semanas. Após isso, não houve diferença estatisticamente significativa entre os grupos experimental e controle entre a oitava e a décima sexta semanas. Houve uma diferença estatisticamente significativa na atividade da fosfatase alcaline e ácida no FCG entre os grupos experimental e controle durante as quatro primeiras semanas de retração dos caninos. Conclusão: As micro-osteoperfurações aumentaram a taxa de movimentação dentária apenas nas primeiras quatro semanas; depois disso, nenhum efeito foi observado na taxa de retração dos caninos após 8, 12 e 16 semanas. Houve aumento considerável na atividade do biomarcador no primeiro mês.