4GRS

Crystal structure of a chimeric DAH7PS

Summary for 4GRS

• Entry DOI: 10.2210/pdb4grs/pdb
• Related: 1ZCO 3PG9
• Descriptor: Phospho-2-dehydro-3-deoxyheptonate aldolase, 2-dehydro-3-deoxyphosphoheptonate aldolase, TYROSINE (3 entities in total)
• Functional Keywords: dahp, dahps, dah7ps, tim barrel, act domain, transferase, allosteric regulation, aromatic biosynthesis, shikimate pathway, transferable allostery
• Biological source: Thermotoga maritima; More
• Total number of polymer chains: 4
• Total formula weight: 149183.51

Authors

Cross, P.J.,Allison, T.M.,Dobson, R.C.J.,Jameson, G.B.,Parker, E.J. (deposition date: 2012-08-26, release date: 2013-02-06, Last modification date: 2023-11-08)

Primary citation

Cross, P.J.,Allison, T.M.,Dobson, R.C.J.,Jameson, G.B.,Parker, E.J.
Engineering allosteric control to an unregulated enzyme by transfer of a regulatory domain
Proc.Natl.Acad.Sci.USA, 110:2111-2116, 2013

PubMed Abstract: Allosteric regulation of protein function is a critical component of metabolic control. Its importance is underpinned by the diversity of mechanisms and its presence in all three domains of life. The first enzyme of the aromatic amino acid biosynthesis, 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, shows remarkable variation in allosteric response and machinery, and both contemporary regulated and unregulated orthologs have been described. To examine the molecular events by which allostery can evolve, we have generated a chimeric protein by joining the catalytic domain of an unregulated 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with the regulatory domain of a regulated enzyme. We demonstrate that this simple gene fusion event on its own is sufficient to confer functional allostery to the unregulated enzyme. The fusion protein shares structural similarities with its regulated parent protein and undergoes an analogous major conformational change in response to the binding of allosteric effector tyrosine to the regulatory domain. These findings help delineate a remarkably facile mechanism for the evolution of modular allostery by domain recruitment.

PubMed: 23345433
DOI: 10.1073/pnas.1217923110

Experimental method

X-RAY DIFFRACTION (3 Å)