以基质金属蛋白酶-12( MMP-12)的晶体结构为模板，采用同源模建方法构建了基质金属蛋白酶-26(MMP-26)的三维结构，并阐明了其S1'结合袋的结构特点， MMP-26中His233残基插入S1'结合袋，限制了S1'结合袋的深度，符合中袋MMPs的特点，因此MMP-26属于中袋MMPs.在此基础上，研究了抑制剂GM6001与MMP-26的相互作用模式，发现GM6001中异羟肟酸结构的羰基氧和羟基氧与催化锌离子发生双齿配位，符合异羟肟酸类MMPs抑制剂的配位特点.%Human matrix metalloproteinase-26 ( MMP-26/endometase/matrilysin-2 ) is a newly identified MMP and its structure has not been reported. With the crystal structure of MMP-12 as structural template, the 3D structure of MMP-26 was built by homology modeling, and S1’ binding pocket characteristics was studied. Residue His233 inserted S1’binding pocket and limited the depth of the pocket, consistent with the interme-diate size prediction. So MMP-26 belongs to intermediate-pocket MMPs. On the basis of the modeling, the in-teractions of inhibition GM6001 with MMP-26 were investigated. Carbonyl oxygen and hydroxyl oxygen of hydroxamic acid structure were in bidentate coordinated mode with catalytic zinc ion, which was consistent with the characteristics of hydroxamic acids MMPs inhibitors. This work suggests that molecular modeling is a useful tool to understand structure-activity relationships and provides new insight for rational inhibitor design that may distinguish MMPs with deep versus intermediate S1’pockets.
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