5LS7

Complex of wild type E. coli alpha aspartate decarboxylase with its processing factor PanZ

Summary for 5LS7

• Entry DOI: 10.2210/pdb5ls7/pdb
• Descriptor: Aspartate 1-decarboxylase, methyl radical, PanD maturation factor, ... (11 entities in total)
• Functional Keywords: protein derived cofactor, coenzyme a biosynthesis, protein complex, metabolic pathway regulation, lyase
• Biological source: Escherichia coli K-12; More
• Cellular location: Cytoplasm : P0A790 P0A790
• Total number of polymer chains: 3
• Total formula weight: 33047.23

Authors

Monteiro, D.C.F.,Webb, M.E.,Pearson, A.R. (deposition date: 2016-08-22, release date: 2017-09-13, Last modification date: 2024-01-17)

Primary citation

Arnott, Z.L.P.,Nozaki, S.,Monteiro, D.C.F.,Morgan, H.E.,Pearson, A.R.,Niki, H.,Webb, M.E.
The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD-PanZAcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan).
Biochemistry, 56:4931-4939, 2017

PubMed Abstract: The 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 β-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 β-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.

PubMed: 28832133
DOI: 10.1021/acs.biochem.7b00509

Experimental method

X-RAY DIFFRACTION (1.16 Å)