Protein Family Models

This entry represents the alpha helical (AH) and Ribosome-InterSubunit (RIS) domains found in RelA/SpoT proteins, adjacent to the ACT domain [1,2]. AH domain interacts with A/R tRNA and links the very C-terminal subdomains with TGS domain. The RIS domain is part of the binding interface between the C-terminal region and the ribosome, bridging the large and the small ribosomal subunits. RIS contains a four-stranded beta-sheet and a short alpha-helix. RelA/SpoT-homologue proteins (RHS) mediate the stringent response in bacteria which enables its metabolic adaptation under stress conditions. These enzymes synthesise the second messenger (p)ppGpp, which is a regulatory metabolite of the stringent response characterised by growth arrest and the modulation of gene expression in response to various nutritional stresses [1-3]. [1]. 27434674. Ribosome*RelA structures reveal the mechanism of stringent response activation. Loveland AB, Bah E, Madireddy R, Zhang Y, Brilot AF, Grigorieff N, Korostelev AA;. Elife. 2016; [Epub ahead of print]. [2]. 32937119. Structural Basis for Regulation of the Opposing (p)ppGpp Synthetase and Hydrolase within the Stringent Response Orchestrator Rel. Pausch P, Abdelshahid M, Steinchen W, Schafer H, Gratani FL, Freibert SA, Wolz C, Turgay K, Wilson DN, Bange G;. Cell Rep. 2020;32:108157. [3]. 15866041. ppGpp: a global regulator in Escherichia coli. Magnusson LU, Farewell A, Nystrom T;. Trends Microbiol. 2005;13:236-242. (from Pfam)

Date:

2024-10-16

ACT domains bind to amino acids and regulate associated enzyme domains. These ACT domains are found at the C-terminus of the RelA protein. (from Pfam)

Date:

2024-08-14

HD domains are metal dependent phosphohydrolases. [1]. 9868367. The HD domain defines a new superfamily of metal-dependent phosphohydrolases. Aravind L, Koonin EV;. Trends Biochem Sci 1998;23:469-472. (from Pfam)

Date:

2024-10-16

This region of unknown function is found in RelA and SpoT of Escherichia coli, and their homologues in plants and in other eubacteria. RelA is a guanosine 3',5'-bis-pyrophosphate (ppGpp) synthetase (EC:2.7.6.5) while SpoT is thought to be a bifunctional enzyme catalysing both ppGpp synthesis and degradation (ppGpp 3'-pyrophosphohydrolase, (EC:3.1.7.2)) [1]. This region is often found in association with HD (Pfam:PF01966), a metal-dependent phosphohydrolase, TGS (Pfam:PF02824) which is a possible nucleotide-binding region, and the ACT regulatory domain (Pfam:PF01842). [1]. 2005134. Residual guanosine 3',5'-bispyrophosphate synthetic activity of relA null mutants can be eliminated by spoT null mutations. Xiao H, Kalman M, Ikehara K, Zemel S, Glaser G, Cashel M;. J Biol Chem 1991;266:5980-5990. (from Pfam)

Date:

2024-10-16

The TGS domain is named after ThrRS, GTPase, and SpoT [1]. Interestingly, TGS domain was detected also at the amino terminus of the uridine kinase from the spirochaete Treponema pallidum (but not any other organism, including the related spirochaete Borrelia burgdorferi). TGS is a small domain that consists of ~50 amino acid residues and is predicted to possess a predominantly beta-sheet structure. There is no direct information on the functions of the TGS domain, but its presence in two types of regulatory proteins (the GTPases and guanosine polyphosphate phosphohydrolases/synthetases) suggests a ligand (most likely nucleotide)-binding, regulatory role [1]. [1]. 10447505. Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events. Wolf YI, Aravind L, Grishin NV, Koonin EV;. Genome Res 1999;9:689-710. [2]. 10319817. The structure of threonyl-tRNA synthetase-tRNA(Thr) complex enlightens its repressor activity and reveals an essential zinc ion in the active site. Sankaranarayanan R, Dock-Bregeon AC, Romby P, Caillet J, Springer M, Rees B, Ehresmann C, Ehresmann B, Moras D;. Cell 1999;97:371-381. (from Pfam)

Date:

2024-10-16

This family of domains generally have a regulatory role. ACT domains are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. Pairs of ACT domains bind specifically to a particular amino acid leading to regulation of the linked enzyme. The ACT domain is found in: D-3-phosphoglycerate dehydrogenase EC:1.1.1.95 Swiss:P08328, which is inhibited by serine [1]. Aspartokinase EC:2.7.2.4 Swiss:P53553, which is regulated by lysine. Acetolactate synthase small regulatory subunit Swiss:P00894, which is inhibited by valine. Phenylalanine-4-hydroxylase EC:1.14.16.1 Swiss:P00439, which is regulated by phenylalanine. Prephenate dehydrogenase EC:4.2.1.51 Swiss:P21203. formyltetrahydrofolate deformylase EC:3.5.1.10, Swiss:P37051, which is activated by methionine and inhibited by glycine. GTP pyrophosphokinase EC:2.7.6.5 Swiss:P11585 [1]. 7719856. The allosteric ligand site in the Vmax-type cooperative enzyme phosphoglycerate dehydrogenase. Schuller DJ, Grant GA, Banaszak LJ;. Nat Struct Biol 1995;2:69-76. Definition of the domain. [2]. 10222208. Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches. Aravind L, Koonin EV;. J Mol Biol 1999;287:1023-1040. (from Pfam)

Date:

2024-10-16

bifunctional (p)ppGpp synthetase/guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase mediates the stringent response by producing and regulating the metabolism of the intracellular signaling alarmone (p)ppGpp

Date:

2017-02-03

(p)ppGpp synthetase; catalyzes the formation of pppGpp and ppGpp from ATP and GTP or GDP

Gene:

relA

Date:

2021-08-24