4byy
Apo GlxR
Structural highlights
FunctionCRPL_CORGL Global transcriptional regulator that complexes with cAMP and binds to specific DNA promoter sites, causing DNA-bending, to regulate transcription. cAMP improves binding to specific DNA sequences, probably by altering protein conformation. Involved in the regulation of gntP and gntK genes, which are involved in gluconate metabolism (PubMed:16385030). May form dimers which bind to the aceB promoter region in the presence of cAMP and repress the glyoxylate bypass genes (PubMed:15150232). It could be a positive regulator of rpf2 gene expression during growth on acetate as the sole carbon source, however because the cytosolic cAMP level is elevated in the presence of glucose and low upon growth on acetate, it is conceivable that it is unable to function as an activator under acetate conditions (PubMed:18355281).[1] [2] [3] Publication Abstract from PubMedThe cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator) transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 A, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 A, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition. The Crystal Structures of Apo and cAMP-Bound GlxR from Corynebacterium glutamicum Reveal Structural and Dynamic Changes upon cAMP Binding in CRP/FNR Family Transcription Factors.,Townsend PD, Jungwirth B, Pojer F, Bussmann M, Money VA, Cole ST, Puhler A, Tauch A, Bott M, Cann MJ, Pohl E PLoS One. 2014 Dec 3;9(12):e113265. doi: 10.1371/journal.pone.0113265., eCollection 2014. PMID:25469635[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
