A QM/MM study on the catalytic mechanism of pyruvate decarboxylase

被引:14
|
作者
Hou, Qianqian [1 ]
Gao, Jun [1 ]
Liu, Yongjun [1 ,2 ]
Liu, Chengbu [1 ]
机构
[1] Shandong Univ, Sch Chem & Chem Engn, Minist Educ, Key Lab Colloid & Interface Chem, Jinan 250100, Shandong, Peoples R China
[2] Chinese Acad Sci, NW Inst Plateau Biol, Key Lab Adaptat & Evolut Plateau Biota, Xining 810001, Qinghai, Peoples R China
基金
中国国家自然科学基金;
关键词
Pyruvate decarboxylase; Decarboxylation; Protonation state; Combined QM/MM; Reaction mechanism; SITE-DIRECTED MUTAGENESIS; ZYMOMONAS-MOBILIS; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; DIPHOSPHATE; ENZYME; RATIONALIZATION; ACTIVATION; PREDICTION; RESOLUTION;
D O I
10.1007/s00214-012-1280-1
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Pyruvate decarboxylase (PDC) is a typical thiamin diphosphate (ThDP)-dependent enzyme with widespread applications in industry. Though studies regarding the reaction mechanism of PDC have been reported, they are mainly focused on the formation of ThDP ylide and some elementary steps in the catalytic cycle, studies about the whole catalytic cycle of PDC are still not completed. In these previous studies, a major controversy is whether the key active residues (Glu473, Glu50', Asp27', His113', His114') are protonated or ionized during the reaction. To explore the catalytic mechanism and the role of key residues in the active site, three whole-enzyme models were considered, and the combined QM/MM calculations on the nonoxidative decarboxylation of pyruvate to acetaldehyde catalyzed by PDC were performed. According to our computational results, the fundamental reaction pathways, the complete energy profiles of the whole catalytic cycle, and the specific role of key residues in the common steps were obtained. It is also found that the same residue with different protonation states will lead to different reaction pathways and energy profiles. The mechanism derived from the model in which the residues (Glu473, Glu50', Asp27', His113', His114') are in their protonated states is most consistent with experimental observations. Therefore, extreme care must be taken when assigning the protonation states in the mechanism study. Because the experimental determination of protonation state is currently difficult, the combined QM/MM method provides an indirect means for determining the active-site protonation state.
引用
收藏
页码:1 / 9
页数:9
相关论文
共 50 条
  • [31] QM/MM investigation of the catalytic mechanism of angiotensin-converting enzyme
    Xia Mu
    Chunchun Zhang
    Dingguo Xu
    Journal of Molecular Modeling, 2016, 22
  • [32] QM/MM investigation of the catalytic mechanism of angiotensin-converting enzyme
    Mu, Xia
    Zhang, Chunchun
    Xu, Dingguo
    JOURNAL OF MOLECULAR MODELING, 2016, 22 (06)
  • [33] Catalytic mechanism of haloalkine dehalogenase: A combined QM/MM study of the initial reaction step.
    Kesavan, LSD
    Gao, JL
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2001, 221 : U412 - U412
  • [34] Insight into Enzymatic Nitrile Reduction: QM/MM Study of the Catalytic Mechanism of QueF Nitrile Reductase
    Ribeiro, Antonio J. M.
    Yang, Lifeng
    Ramos, Maria J.
    Fernandes, Pedro A.
    Liang, Zhao-Xun
    Hirao, Hajime
    ACS CATALYSIS, 2015, 5 (06): : 3740 - 3751
  • [35] QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH)
    Wenyou Zhu
    Yongjun Liu
    Theoretical Chemistry Accounts, 2014, 133
  • [36] QM/MM Study of Human Transketolase: Thiamine Diphosphate Activation Mechanism and Complete Catalytic Cycle
    Nauton, Lionel
    Hecquet, Laurence
    Thery, Vincent
    JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2021, 61 (07) : 3502 - 3515
  • [37] QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH)
    Zhu, Wenyou
    Liu, Yongjun
    THEORETICAL CHEMISTRY ACCOUNTS, 2013, 133 (02) : 1 - 9
  • [38] QM/MM study on the catalytic mechanism of benzene hydroxylation over Fe-ZSM-5
    Shiota, Yoshihito
    Suzuki, Kunihiko
    Yoshizawa, Kazunari
    ORGANOMETALLICS, 2006, 25 (13) : 3118 - 3123
  • [39] QM/MM study on the mechanism of peptide hydrolysis by carboxypeptidase A
    Szeto, Michelle W. Y.
    Mujika, Jon I.
    Zurek, Jolanta
    Mulholland, Adrian J.
    Harvey, Jeremy N.
    JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 2009, 898 (1-3): : 106 - 114
  • [40] The reaction mechanism of hydroxyethylphosphonate dioxygenase: a QM/MM study
    Du, Likai
    Gao, Jun
    Liu, Yongjun
    Zhang, Dongju
    Liu, Chengbu
    ORGANIC & BIOMOLECULAR CHEMISTRY, 2012, 10 (05) : 1014 - 1024