Avila Rodríguez Maria Isabela, Velez Rueda Ana Julia, Hernández-Pérez Jesús, Benavides Jorge, Sanchez Mirna Lorena
Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Ave. Eugenio Garza Sada, 2501, Monterrey, Nuevo León C.P 64849, Mexico.
Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes - CONICET, Roque Sáenz Peña 352, Bernal, Buenos Aires B1876, Argentina.
Comput Struct Biotechnol J. 2024 Oct 11;23:3680-3691. doi: 10.1016/j.csbj.2024.10.015. eCollection 2024 Dec.
Chronic wounds and burns are a worldwide healthcare problem that erodes patients' well-being and healthcare systems. This silent and costly epidemic requires new, cost-efficient solutions to improve patients' physical and economic welfare. Eschar-degrading vegetal and bacterial proteases have been utilized as a solution. However, these proteins are evolutionarily far from those present in human wound healing. Serine protease (SP) and annexin (ANX) proteins interact within the skin healing process. A homology-based identification pipeline can help in discovering selective human SP and ANX analogs in the epithelial tissue of the fast-healing species, . In the present work, we found 14 candidates for RT-PCR in using homology inference. The genetically detected candidates were then structurally and sequentially analyzed to understand their possible relation to SPs and ANXs involved in human wound healing. A total of six TBLASTN/BLASTX candidates (four SPs and two ANXs) were detected in skin. Structural analysis revealed that all SP candidates resembled human KLK4, KLK5, KLK6, and KLK8, whereas all ANX only resembled human ANXA4. Structure and sequence analysis revealed high conservation of ANX Ca binding sites (GDXD) and SP catalytic triad (HDS) motifs. In addition, structural analysis revealed that SP substrate selectivity position 186 was the main difference between human KLK5 and SPs. These findings may allow the proposal and testing of more selective formulations, broadening treatments beyond debridement.
慢性伤口和烧伤是一个全球性的医疗保健问题，侵蚀着患者的健康和医疗系统。这种悄无声息且代价高昂的流行病需要新的、具有成本效益的解决方案来改善患者的身体和经济福祉。已利用能降解焦痂的植物和细菌蛋白酶作为一种解决方案。然而，这些蛋白质在进化上与人类伤口愈合中存在的蛋白质相去甚远。丝氨酸蛋白酶（SP）和膜联蛋白（ANX）在皮肤愈合过程中相互作用。基于同源性的识别流程有助于在快速愈合物种的上皮组织中发现选择性的人类SP和ANX类似物。在本研究中，我们通过同源性推断在[具体物种]中发现了14个用于逆转录聚合酶链反应（RT-PCR）的候选物。然后对基因检测到的候选物进行结构和序列分析，以了解它们与人类伤口愈合中涉及的SP和ANX的可能关系。在[具体物种]皮肤中总共检测到6个通过TBLASTN/BLASTX分析得到的候选物（4个SP和2个ANX）。结构分析表明，所有SP候选物都类似于人类组织激肽释放酶4（KLK4）、KLK5、KLK6和KLK8，而所有ANX仅类似于人类膜联蛋白A4（ANXA4）。结构和序列分析揭示了ANX钙结合位点（GDXD）和SP催化三联体（HDS）基序的高度保守性。此外，结构分析表明，SP底物选择性位置186是人类KLK5和[具体物种]的SP之间的主要区别。这些发现可能有助于提出和测试更具选择性的配方，将治疗范围扩大到清创术之外。
