Porto William F, Nolasco Diego O, Pires Állan S, Pereira Rinaldo W, Franco Octávio L, Alencar Sérgio A
Programa De Pós-Graduação Em Ciências Genômicas E Biotecnologia, Universidade Católica De Brasília, Brasília, DF, Brazil.
Centro De Análises Proteômicas E Bioquímicas, Pós-Graduação Em Ciências Genômicas E Biotecnologia, Universidade Católica De Brasília, Brasília, DF, Brazil.
Biopolymers. 2016 Sep;106(5):633-44. doi: 10.1002/bip.22866.
Defensins confer host defense against microorganisms and are important for human health. Single nucleotide polymorphisms (SNPs) in defensin gene-coding regions could lead to less active variants. Using SNP data available at the dbSNP database and frequency information from the 1000 Genomes Project, two DEFA5 (L26I and R13H) and eight DEFB1 (C35S, K31T, K33R, R29G, V06I, C12Y, Y28* and C05*) missense and nonsense SNPs that are located within mature regions of the coded defensins were retrieved. Such SNPs are rare and population restricted. In order to assess their antibacterial activity against Escherichia coli, two linear regression models were used from a previous work, which models the antibacterial activity as a function of solvation potential energy, using molecular dynamics data. Regarding only the antibacterial predictions, for HD5, no biological differences between wild-type and its variants were observed; while for HBD1, the results suggest that the R29G, K31T, Y28* and C05* variants could be less active than the wild-type one. The data here reported could lead to a substantial improvement in knowledge about the impact of missense SNPs in human defensins and their world distribution. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 633-644, 2016.
防御素赋予宿主抵抗微生物的能力，对人类健康至关重要。防御素基因编码区域的单核苷酸多态性（SNP）可能导致活性较低的变体。利用dbSNP数据库中的SNP数据和千人基因组计划的频率信息，检索出位于编码防御素成熟区域内的两个DEFA5（L26I和R13H）以及八个DEFB1（C35S、K31T、K33R、R29G、V06I、C12Y、Y28和C05）错义及无义SNP。这些SNP较为罕见且具有人群局限性。为了评估它们对大肠杆菌的抗菌活性，采用了之前工作中的两个线性回归模型，该模型利用分子动力学数据将抗菌活性作为溶剂化势能的函数进行建模。仅就抗菌预测而言，对于HD5，未观察到野生型与其变体之间的生物学差异；而对于HBD1，结果表明R29G、K31T、Y28和C05变体的活性可能低于野生型。本文报道的数据可能会大幅增进我们对人类防御素中错义SNP的影响及其全球分布的了解。© 2016威利期刊公司。生物聚合物（肽科学）106: 633 - 644，2016年。
