Atomic resolution crystal structure of Sapp2p, a secreted aspartic protease from Candida parapsilosis.

IF 2.2 4区生物学

Acta Crystallographica Section D: Biological Crystallography Pub Date : 2015-12-01 DOI:10.1107/S1399004715019392

J. Dostál, Adam Pecina, O. Hrušková-Heidingsfeldová, L. Marečková, I. Pichová, P. Řezáčová, M. Lepšík, J. Brynda

引用次数: 10

Abstract

The virulence of the Candida pathogens is enhanced by the production of secreted aspartic proteases, which therefore represent possible targets for drug design. Here, the crystal structure of the secreted aspartic protease Sapp2p from Candida parapsilosis was determined. Sapp2p was isolated from its natural source and crystallized in complex with pepstatin A, a classical aspartic protease inhibitor. The atomic resolution of 0.83 Å allowed the protonation states of the active-site residues to be inferred. A detailed comparison of the structure of Sapp2p with the structure of Sapp1p, the most abundant C. parapsilosis secreted aspartic protease, was performed. The analysis, which included advanced quantum-chemical interaction-energy calculations, uncovered molecular details that allowed the experimentally observed equipotent inhibition of both isoenzymes by pepstatin A to be rationalized.

查看原文本刊更多论文

假丝酵素分泌的天冬氨酸蛋白酶Sapp2p的原子分辨率晶体结构。

念珠菌病原体的毒力通过分泌天冬氨酸蛋白酶的产生而增强，因此天冬氨酸蛋白酶代表了药物设计的可能目标。本文测定了假丝酵母旁裂菌分泌的天冬氨酸蛋白酶Sapp2p的晶体结构。从天然来源中分离出Sapp2p，并与经典的天冬氨酸蛋白酶抑制剂pepstatin A配合结晶。0.83 Å的原子分辨率可以推断活性位点残基的质子化状态。对Sapp2p的结构与Sapp1p的结构进行了详细的比较，Sapp1p是最丰富的parapsilo分泌的天冬氨酸蛋白酶。该分析包括先进的量子化学相互作用能计算，揭示了分子细节，使实验观察到的胃抑素A对两种同工酶的等效抑制得以合理解释。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Acta Crystallographica Section D: Biological Crystallography 生物-晶体学

自引率

13.60%

发文量

审稿时长

3 months

期刊介绍： Acta Crystallographica Section D welcomes the submission of articles covering any aspect of structural biology, with a particular emphasis on the structures of biological macromolecules or the methods used to determine them. Reports on new structures of biological importance may address the smallest macromolecules to the largest complex molecular machines. These structures may have been determined using any structural biology technique including crystallography, NMR, cryoEM and/or other techniques. The key criterion is that such articles must present significant new insights into biological, chemical or medical sciences. The inclusion of complementary data that support the conclusions drawn from the structural studies (such as binding studies, mass spectrometry, enzyme assays, or analysis of mutants or other modified forms of biological macromolecule) is encouraged. Methods articles may include new approaches to any aspect of biological structure determination or structure analysis but will only be accepted where they focus on new methods that are demonstrated to be of general applicability and importance to structural biology. Articles describing particularly difficult problems in structural biology are also welcomed, if the analysis would provide useful insights to others facing similar problems.