This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
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
3tfc is a 2 chain structure with sequence from Listeria monocytogenes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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.
Structural analysis of a 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with an N-terminal chorismate mutase-like regulatory domain.,Light SH, Halavaty AS, Minasov G, Shuvalova L, Anderson WF Protein Sci. 2012 Apr 13. doi: 10.1002/pro.2075. PMID:22505283[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑ Light SH, Halavaty AS, Minasov G, Shuvalova L, Anderson WF. Structural analysis of a 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with an N-terminal chorismate mutase-like regulatory domain. Protein Sci. 2012 Apr 13. doi: 10.1002/pro.2075. PMID:22505283 doi:10.1002/pro.2075
