6m2u

The crystal structure of benzoate coenzyme A ligase double mutant (H333A/I334A) in complex with 2-chloro-1,3-thiazole-5-carboxylate-AMP

spinqualitylabelsall models 6m2u, resolution 1.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6m2u is a 2 chain structure with sequence from Rhodopseudomonas palustris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.709Å Ligands: AMP, F0O Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q93TK0_RHOPL Publication Abstract from PubMed 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 Pinus Sylvestris, 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 Rhodopseudomonas palustris in an apo 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 A, 1.7 A, and 2.13 A, 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. Chemoenzymatic Synthesis and Biological Evaluation for Bioactive Molecules Derived from Bacterial Benzoyl Coenzyme A Ligase and Plant Type III Polyketide Synthase.,Adhikari K, Lo IW, Chen CL, Wang YL, Lin KH, Zadeh SM, Rattinam R, Li YS, Wu CJ, Li TL Biomolecules. 2020 May 9;10(5). pii: biom10050738. doi: 10.3390/biom10050738. PMID:32397467 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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