Azhagiya Singam E R, Rajapandian V, Subramanian V
Chemical Laboratory, Council of Scientific and Industrial Research, Central Leather Research Institute, Adyar, Chennai, 600 020, Tamil Nadu, India.
Biopolymers. 2014 Jul;101(7):779-94. doi: 10.1002/bip.22457.
Although several models have been proposed for the interaction of collagen with gelatinase-A (matrix metalloproteinases-2 (MMP-2)), the extensive role of each domain of gelatinase A in hydrolyzing the collagens with and without interruptions is still elusive. Molecular docking, molecular dynamics (MD) simulation, normal mode analysis (NMA) and framework rigidity optimized dynamics algorithm (FRODAN) based analysis were carried out to understand the function of various domains of MMP-2 upon interaction with collagen like peptides. The results reveal that the collagen binding domain (CBD) binds to the C-terminal of collagen like peptide with interruption. CBD helps in unwinding the loosely packed interrupted region of triple helical structure to a greater extent. It can be possible to speculate that the role of hemopexin (HPX) domain is to prevent further unwinding of collagen like peptide by binding to the other end of the collagen like peptide. The catalytic (CAT) domain then reorients itself to interact with the part of the unwound region of collagen like peptide for further hydrolysis. In conclusion the CBD of MMP-2 recognizes the collagen and aids in unwinding the collagen like peptide with interruptions, and the HPX domain of MMP-2 binds to the other end of the collagen allowing CAT domain to access the cleavage site. This study provides a comprehensive understanding of the structural basis of collagenolysis by MMP-2.
尽管已经提出了几种胶原蛋白与明胶酶-A（基质金属蛋白酶-2，即MMP-2）相互作用的模型，但明胶酶A的每个结构域在水解有或无中断的胶原蛋白时所起的广泛作用仍不清楚。进行了基于分子对接、分子动力学（MD）模拟、简正模式分析（NMA）和框架刚性优化动力学算法（FRODAN）的分析，以了解MMP-2各个结构域与类胶原蛋白肽相互作用时的功能。结果表明，胶原蛋白结合结构域（CBD）与有中断的类胶原蛋白肽的C末端结合。CBD有助于在更大程度上解开三螺旋结构中松散堆积的中断区域。可以推测，血红素结合蛋白（HPX）结构域的作用是通过与类胶原蛋白肽的另一端结合来防止类胶原蛋白肽进一步解旋。然后催化（CAT）结构域重新定位自身，与类胶原蛋白肽解旋区域的一部分相互作用以进行进一步水解。总之，MMP-2的CBD识别胶原蛋白并有助于解开有中断的类胶原蛋白肽，而MMP-2的HPX结构域与胶原蛋白的另一端结合，使CAT结构域能够进入切割位点。本研究提供了对MMP-2胶原降解结构基础的全面理解。
