1kfl

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spinqualitylabelsall models 1kfl, resolution 2.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of phenylalanine-regulated 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHP synthase) from E.coli complexed with Mn2+, PEP, and Phe

Overview

3-Deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS), the first, enzyme of the aromatic biosynthetic pathway in microorganisms and plants, catalyzes the aldol-like condensation of phosphoenolpyruvate and, D-erythrose-4-phosphate with the formation of, 3-deoxy-D-arabino-heptulosonate-7-phosphate. In Escherichia coli, there, are three isoforms of DAHPS, each specifically feedback-regulated by one, of the three aromatic amino acid end products. The crystal structure of, the phenylalanine-regulated DAHPS from E.coli in complex with its, inhibitor, L-phenylalanine, phosphoenolpyruvate, and metal cofactor, Mn(2+), has been determined to 2.8A resolution. Phe binds in a cavity, formed by residues of two adjacent subunits and is located about 20A from, the closest active site. A model for the mechanism of allosteric, inhibition has been derived from conformational differences between the, Phe-bound and previously determined Phe-free structures. Two interrelated, paths of conformational changes transmit the inhibitory signal from the, Phe-binding site to the active site of DAHPS. The first path involves, transmission within a single subunit due to the movement of adjacent, segments of the protein. The second involves alterations in the contacts, between subunits. The combination of these two paths changes the, conformation of one of the active site loops significantly and shifts the, other slightly. This alters the interaction of DAHPS with both of its, substrates. Upon binding of Phe, the enzyme loses the ability to bind, D-erythrose-4-phosphate and binds phosphoenolpyruvate in a flipped, orientation.

About this Structure

1KFL is a Single protein structure of sequence from Escherichia coli with MN, SO4, PHE and PEP as ligands. Active as 3-deoxy-7-phosphoheptulonate synthase, with EC number 2.5.1.54 Full crystallographic information is available from OCA.

Reference

Allosteric inhibition of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase alters the coordination of both substrates., Shumilin IA, Zhao C, Bauerle R, Kretsinger RH, J Mol Biol. 2002 Jul 26;320(5):1147-56. PMID:12126632

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