5ls7
From Proteopedia
Complex of wild type E. coli alpha aspartate decarboxylase with its processing factor PanZ
Structural highlights
Function[PAND_ECOLI] Catalyzes the pyruvoyl-dependent decarboxylation of aspartate to produce beta-alanine.[1] [PANZ_ECOLI] Controls both the activation and catalytic activity of PanD in a coenzyme A (CoA)-dependent fashion. Binding of CoA or a derivative to PanZ leads to interaction with PanD, which promotes the processing and activation of pro-PanD, and subsequent substrate-mediated inhibition of the active form of PanD (PubMed:23170229, PubMed:25910242). Inhibition of PanD activity is probably the primary metabolic role of PanZ, allowing negative feedback regulation of pantothenate biosynthesis by CoA (PubMed:25910242).[2] [3] Publication Abstract from PubMedThe antimetabolite pentyl pantothenamide has broad spectrum antibiotic activity but exhibits enhanced activity against Escherichia coli. The PanDZ complex has been proposed to regulate the pantothenate biosynthetic pathway in E. coli by limiting the supply of beta-alanine in response to coenzyme A concentration. We show that formation of such a complex between activated aspartate decarboxylase (PanD) and PanZ leads to sequestration of the pyruvoyl cofactor as a ketone hydrate and demonstrate that both PanZ overexpression-linked beta-alanine auxotrophy and pentyl pantothenamide toxicity are due to formation of this complex. This both demonstrates that the PanDZ complex regulates pantothenate biosynthesis in a cellular context and validates the complex as a target for antibiotic development. The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD-PanZ.AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan).,Arnott ZLP, Nozaki S, Monteiro DCF, Morgan HE, Pearson AR, Niki H, Webb ME Biochemistry. 2017 Sep 7. doi: 10.1021/acs.biochem.7b00509. PMID:28832133[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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