The dimerization domain in DapE enzymes is required for catalysis.
The dimerization domain in DapE enzymes is required for catalysis.
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DOI：
10.1371/journal.pone.0093593
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Holz RC
中科院分区：
文献类型：
--
作者：
Nocek B;Starus A;Makowska-Grzyska M;Gutierrez B;Sanchez S;Jedrzejczak R;Mack JC;Olsen KW;Joachimiak A;Holz RC
The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Therefore dap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) converts N-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role of each domain of the enzyme we engineered dimerization domain deletion mutants of DapEs from Haemophilus influenzae and Vibrio cholerae, and characterized these proteins structurally and biochemically. No activity was observed for all deletion mutants. Structural comparisons of wild-type, inactive monomeric DapE enzymes with other M20 peptidases suggest that the dimerization domain is essential for DapE enzymatic activity. Structural analysis and molecular dynamics simulations indicate that removal of the dimerization domain increased the flexibility of a conserved active site loop that may provide critical interactions with the substrate.
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DOI：
10.1074/jbc.m110.147579
发表时间：
2010-09-17
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Girish TS;Gopal B
通讯作者：
Gopal B
影响因子：
4.8
作者：
Kim, Youngchang;Babnigg, Gyorgy;Jedrzejczak, Robert;Eschenfeldt, William H.;Li, Hui;Maltseva, Natalia;Hatzos-Skintges, Catherine;Gu, Minyi;Makowska-Grzyska, Magdalena;Wu, Ruiying;An, Hao;Chhor, Gekleng;Joachimiak, Andrzej
通讯作者：
Joachimiak, Andrzej
影响因子：
2.9
作者：
Bienvenue, DL;Gilner, DM;Holz, RC
通讯作者：
Holz, RC
影响因子：
3
作者：
Gillner, Danuta M.;Bienvenue, David L.;Nocek, Boguslaw P.;Joachimiak, Andrzej;Zachary, Vincentos;Bennett, Brian;Holz, Richard C.
通讯作者：
Holz, Richard C.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH