机构:[1]Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, 650091 Yunnan, P. R. China[2]Department of Cardiology, No. 1 Affiliated Hospital, Kunming Medical College, Kunming, 650032 Yunnan, P. R. China内科科室心脏内科昆明医科大学附属第一医院云南省第一人民医院[3]Human Genetics Center, School of Public Health, University of Texas, 1400 Herman Pressler, E453, Houston, TX 77025, USA
Serine protease proteinase K, a member of the subtilisin family of enzymes, is of significant industrial, agricultural and biotechnological importance. Despite the wealth of structural information about proteinase K provided by static X-ray structures, a full understanding of the enzymatic mechanism requires further insight into the dynamic properties of this enzyme. Molecular dynamics simulations and essential dynamics (ED) analysis were performed to investigate the molecular motions in proteinase K. The results indicate that the internal core of proteinase K is relatively rigid, whereas the surface-exposed loops, most notably the substrate-binding regions, exhibit considerable conformational fluctuations. Further ED analysis reveals that the large concerted motions in the substrate-binding regions cause opening/closing of the substrate-binding pockets, thus supporting the proposed induced-fit mechanism of substrate binding. The distinct electrostatic/hydrogen-bonding interactions between Asp39 and His69 and between His69 and Ser224 within the catalytic triad lead to different thermal motions and orientations of these three catalytic residues, which can be related to their different functional roles in the catalytic process. Statistical analyses of the geometrical/functional properties as well as evolutionary conservation of the glycines in proteinase K-like proteins reveal that glycines may play an important role in determining the folding architecture and structural flexibility of this class of enzymes. Our simulation study complements the biochemical and structural studies and provides new insights into the dynamic structural basis of the functional properties of this class of enzymes.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [30630003, 30860011]; Yunnan Province [2006C008M, 2007C163M, 07Z10756, 2007PY-22, 08Y0026]; Yunnan University [KL070002]
第一作者机构:[1]Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, 650091 Yunnan, P. R. China
通讯作者:
推荐引用方式(GB/T 7714):
Liu Shu-Qun,Meng Zhao-Hui,Fu Yun-Xin,et al.Insights derived from molecular dynamics simulation into the molecular motions of serine protease proteinase K[J].JOURNAL OF MOLECULAR MODELING.2010,16(1):17-28.doi:10.1007/s00894-009-0518-x.
APA:
Liu, Shu-Qun,Meng, Zhao-Hui,Fu, Yun-Xin&Zhang, Ke-Qin.(2010).Insights derived from molecular dynamics simulation into the molecular motions of serine protease proteinase K.JOURNAL OF MOLECULAR MODELING,16,(1)
MLA:
Liu, Shu-Qun,et al."Insights derived from molecular dynamics simulation into the molecular motions of serine protease proteinase K".JOURNAL OF MOLECULAR MODELING 16..1(2010):17-28