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REFMAC5 for the refinement of macromolecular crystal structures.用于大分子晶体结构精修的REFMAC5
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Matrix metalloproteinase inhibitors: a critical appraisal of design principles and proposed therapeutic utility.基质金属蛋白酶抑制剂：设计原则的批判性评价及提出的治疗用途。
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Molecular replacement with MOLREP.使用MOLREP进行分子置换。
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Reduced incidence and severity of experimental autoimmune arthritis in mice expressing catalytically inactive A disintegrin and metalloproteinase 8 (ADAM8).在表达催化失活的解整合素金属蛋白酶8（ADAM8）的小鼠中，实验性自身免疫性关节炎的发病率和严重程度降低。
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ADAM-8 isolated from human osteoarthritic chondrocytes cleaves fibronectin at Ala(271).从人骨关节炎软骨细胞中分离出的ADAM-8在丙氨酸271处切割纤连蛋白。
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ADAM8 and its single nucleotide polymorphism 2662 T/G are associated with advanced atherosclerosis and fatal myocardial infarction: Tampere vascular study.ADAM8 及其单核苷酸多态性 2662 T/G 与晚期动脉粥样硬化和致命性心肌梗死相关：坦佩雷血管研究。
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ADAM8 is selectively up-regulated in endothelial cells and is associated with angiogenesis after spinal cord injury in adult mice.ADAM8在成年小鼠脊髓损伤后的内皮细胞中选择性上调，并与血管生成相关。
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Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket.新型异羟肟酸酯作为高效肿瘤坏死因子-α转化酶抑制剂的发现。第二部分：S3'口袋的优化。
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Autoactivation of human ADAM8: a novel pre-processing step is required for catalytic activity.人ADAM8的自激活：催化活性需要一个新的预处理步骤。
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与batimastat复合的人ADAM-8催化结构域的结构

Structure of human ADAM-8 catalytic domain complexed with batimastat.

作者信息

Hall Troii, Shieh Huey Sheng, Day Jacqueline E, Caspers Nicole, Chrencik Jill E, Williams Jennifer M, Pegg Lyle E, Pauley Adele M, Moon Andrea F, Krahn Joseph M, Fischer David H, Kiefer James R, Tomasselli Alfredo G, Zack Marc D

机构信息

Pfizer Inc, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA.

出版信息

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Jun 1;68(Pt 6):616-21. doi: 10.1107/S1744309112015618. Epub 2012 May 22.

DOI:10.1107/S1744309112015618
PMID:22684055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3370895/
Abstract

The role of ADAM-8 in cancer and inflammatory diseases such as allergy, arthritis and asthma makes it an attractive target for drug development. Therefore, the catalytic domain of human ADAM-8 was expressed, purified and crystallized in complex with a hydroxamic acid inhibitor, batimastat. The crystal structure of the enzyme-inhibitor complex was refined to 2.1 Å resolution. ADAM-8 has an overall fold similar to those of other ADAM members, including a central five-stranded β-sheet and a catalytic Zn(2+) ion. However, unique differences within the S1' binding loop of ADAM-8 are observed which might be exploited to confer specificity and selectivity to ADAM-8 competitive inhibitors for the treatment of diseases involving this enzyme.

摘要

ADAM-8在癌症以及诸如过敏、关节炎和哮喘等炎症性疾病中所起的作用，使其成为药物研发的一个有吸引力的靶点。因此，人ADAM-8的催化结构域得以表达、纯化，并与一种异羟肟酸抑制剂batimastat形成复合物后进行结晶。该酶-抑制剂复合物的晶体结构被精修至2.1 Å的分辨率。ADAM-8的整体折叠结构与其他ADAM家族成员相似，包括一个中心的五链β-折叠片层和一个催化性Zn(2+)离子。然而，在ADAM-8的S1'结合环内观察到了独特的差异，这些差异可能被用于赋予ADAM-8竞争性抑制剂特异性和选择性，以治疗涉及该酶的疾病。