CAJ | 학술논문

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.
이기질금속단백매-12( MMP-12)적정체결구위모판，채용동원모건방법구건료기질금속단백매-26(MMP-26)적삼유결구，병천명료기S1'결합대적결구특점， MMP-26중His233잔기삽입S1'결합대，한제료S1'결합대적심도，부합중대MMPs적특점，인차MMP-26속우중대MMPs.재차기출상，연구료억제제GM6001여MMP-26적상호작용모식，발현GM6001중이간우산결구적탄기양화간기양여최화자리자발생쌍치배위，부합이간우산류MMPs억제제적배위특점.
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.