6M2U
The crystal structure of benzoate coenzyme A ligase double mutant (H333A/I334A) in complex with 2-chloro-1,3-thiazole-5-carboxylate-AMP
Summary for 6M2U
| Entry DOI | 10.2210/pdb6m2u/pdb |
| Descriptor | Benzoate-coenzyme A ligase, ADENOSINE MONOPHOSPHATE, 2-chloranyl-1,3-thiazole-5-carboxylic acid, ... (4 entities in total) |
| Functional Keywords | benzoate, coenzyme, complex, ligase |
| Biological source | Rhodopseudomonas palustris |
| Total number of polymer chains | 2 |
| Total formula weight | 113356.61 |
| Authors | Li, T.L.,Adhikari, K. (deposition date: 2020-02-29, release date: 2021-01-13, Last modification date: 2023-11-29) |
| Primary citation | Adhikari, K.,Lo, I.W.,Chen, C.L.,Wang, Y.L.,Lin, K.H.,Zadeh, S.M.,Rattinam, R.,Li, Y.S.,Wu, C.J.,Li, T.L. Chemoenzymatic Synthesis and Biological Evaluation for Bioactive Molecules Derived from Bacterial Benzoyl Coenzyme A Ligase and Plant Type III Polyketide Synthase. Biomolecules, 10:-, 2020 Cited by PubMed Abstract: Plant type III polyketide synthases produce diverse bioactive molecules with a great medicinal significance to human diseases. Here, we demonstrated versatility of a stilbene synthase (STS) from , which can accept various non-physiological substrates to form unnatural polyketide products. Three enzymes (4-coumarate CoA ligase, malonyl-CoA synthetase and engineered benzoate CoA ligase) along with synthetic chemistry was practiced to synthesize starter and extender substrates for STS. Of these, the crystal structures of benzoate CoA ligase (BadA) from in an form or in complex with a 2-chloro-1,3-thiazole-5-carboxyl-AMP or 2-methylthiazole-5-carboxyl-AMP intermediate were determined at resolutions of 1.57 Å, 1.7 Å, and 2.13 Å, respectively, which reinforces its capacity in production of unusual CoA starters. STS exhibits broad substrate promiscuity effectively affording structurally diverse polyketide products. Seven novel products showed desired cytotoxicity against a panel of cancer cell lines (A549, HCT116, Cal27). With the treatment of two selected compounds, the cancer cells underwent cell apoptosis in a dose-dependent manner. The precursor-directed biosynthesis alongside structure-guided enzyme engineering greatly expands the pharmaceutical repertoire of lead compounds with promising/enhanced biological activities. PubMed: 32397467DOI: 10.3390/biom10050738 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.709 Å) |
Structure validation
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