1ESN

STRUCTURAL BASIS FOR THE FEEDBACK REGULATION OF ESCHERICHIA COLI PANTOTHENATE KINASE BY COENZYME A

Summary for 1ESN

• Entry DOI: 10.2210/pdb1esn/pdb
• Related: 1ESM
• Descriptor: PANTOTHENATE KINASE, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: protein-inhibitor complex, transferase
• Biological source: Escherichia coli
• Cellular location: Cytoplasm (Probable): P0A6I3
• Total number of polymer chains: 4
• Total formula weight: 149057.90

Authors

Yun, M.,Park, C.G.,Kim, J.Y.,Rock, C.O.,Jackowski, S.,Park, H.W. (deposition date: 2000-04-10, release date: 2000-11-17, Last modification date: 2011-07-13)

Primary citation

Yun, M.,Park, C.G.,Kim, J.Y.,Rock, C.O.,Jackowski, S.,Park, H.W.
Structural basis for the feedback regulation of Escherichia coli pantothenate kinase by coenzyme A.
J.Biol.Chem., 275:28093-28099, 2000

PubMed Abstract: Pantothenate kinase (PanK) is a key regulatory enzyme in the coenzyme A (CoA) biosynthetic pathway and catalyzes the phosphorylation of pantothenic acid to form phosphopantothenate. CoA is a feedback inhibitor of PanK activity by competitive binding to the ATP site. The structures of the Escherichia coli enzyme, in complex with a nonhydrolyzable analogue of ATP, 5'-adenylimido-diphosphate (AMPPNP), or with CoA, were determined at 2.6 and 2.5 A, respectively. Both structures show that two dimers occupy an asymmetric unit; each subunit has a alpha/beta mononucleotide-binding fold with an extensive antiparallel coiled coil formed by two long helices along the dimerization interface. The two ligands, AMPPNP and CoA, associate with PanK in very different ways, but their phosphate binding sites overlap, explaining the kinetic competition between CoA and ATP. Residues Asp(127), His(177), and Arg(243) are proposed to be involved in catalysis, based on modeling of the pentacoordinate transition state. The more potent inhibition by CoA, compared with the CoA thioesters, is explained by a tight interaction of the CoA thiol group with the side chains of aromatic residues, which is predicted to discriminate against the CoA thioesters. The PanK structure provides the framework for a more detailed understanding of the mechanism of catalysis and feedback regulation of PanK.

PubMed: 10862768

Experimental method

X-RAY DIFFRACTION (2.6 Å)