3TFC

1.95 Angstrom crystal structure of a bifunctional 3-deoxy-7-phosphoheptulonate synthase/chorismate mutase (aroA) from Listeria monocytogenes EGD-e in complex with phosphoenolpyruvate

Summary for 3TFC

• Entry DOI: 10.2210/pdb3tfc/pdb
• Descriptor: 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, MANGANESE (II) ION, PHOSPHOENOLPYRUVATE, ... (5 entities in total)
• Functional Keywords: structural genomics, center for structural genomics of infectious diseases, csgid, (beta/alpha) barrel, tim barrel, transferase-isomerase complex, transferase/isomerase
• Biological source: Listeria monocytogenes
• Total number of polymer chains: 2
• Total formula weight: 85472.26

Authors

Light, S.H.,Minasov, G.,Halavaty, A.S.,Shuvalova, L.,Kwon, K.,Anderson, W.F.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2011-08-15, release date: 2011-08-31, Last modification date: 2024-02-28)

Primary citation

Light, S.H.,Halavaty, A.S.,Minasov, G.,Shuvalova, L.,Anderson, W.F.
Structural analysis of a 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with an N-terminal chorismate mutase-like regulatory domain.
Protein Sci., 21:887-895, 2012

PubMed Abstract: 3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS) catalyzes the first step in the biosynthesis of a number of aromatic metabolites. Likely because this reaction is situated at a pivotal biosynthetic gateway, several DAHPS classes distinguished by distinct mechanisms of allosteric regulation have independently evolved. One class of DAHPSs contains a regulatory domain with sequence homology to chorismate mutase-an enzyme further downstream of DAHPS that catalyzes the first committed step in tyrosine/phenylalanine biosynthesis-and is inhibited by chorismate mutase substrate (chorismate) and product (prephenate). Described in this work, structures of the Listeria monocytogenes chorismate/prephenate regulated DAHPS in complex with Mn(2+) and Mn(2+) + phosphoenolpyruvate reveal an unusual quaternary architecture: DAHPS domains assemble as a tetramer, from either side of which chorismate mutase-like (CML) regulatory domains asymmetrically emerge to form a pair of dimers. This domain organization suggests that chorismate/prephenate binding promotes a stable interaction between the discrete regulatory and catalytic domains and supports a mechanism of allosteric inhibition similar to tyrosine/phenylalanine control of a related DAHPS class. We argue that the structural similarity of chorismate mutase enzyme and CML regulatory domain provides a unique opportunity for the design of a multitarget antibacterial.

PubMed: 22505283
DOI: 10.1002/pro.2075

Experimental method

X-RAY DIFFRACTION (1.95 Å)