ACT domain proteins similar to the yet uncharacterized Streptococcus pneumoniae ACT domain protein; This CD, ACT_1ZPV, includes those single ACT domain proteins similar to the yet uncharacterized Streptococcus pneumoniae ACT domain protein (pdb structure 1ZPV). Members of this CD belong to the superfamily of ACT regulatory domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307615087  8 KAIMTVTGLDHTGIIAAVSQTLASQRVNIVNVSQTLMDEYFTMIMLLEFDPEVVSLRALQDAMKSVETAERLEIRVQAEA 87
Cdd:cd04872   1 KAVITVVGKDRVGIVAGVSTKLAELNVNILDISQTIMDGYFTMIMIVDISESNLDFAELQEELEELGKELGVKIRIQHED 80

                ....*...
gi 307615087 88 IFNTMHSL 95
Cdd:cd04872  81 IFKAMHRI 88

ACT domain; ACT domains bind to amino acids and regulate associated enzyme domains.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 307615087  10 IMTVTGLDHTGIIAAVSQTLASQRVNIVNVSQTLMDEYFTMIMLLEFDPEVVSlrALQDAMKSVETAERLEIRVQ 84
Cdd:pfam13740  4 LITATGPDRPGLTASLTAVLAEHGCNILDSGQAVIHNRLSLGLLVSGPWDALA--RLEKDLLFLAHELGLTVRFK 76

ACT domain proteins similar to the yet uncharacterized Streptococcus pneumoniae ACT domain protein; This CD, ACT_1ZPV, includes those single ACT domain proteins similar to the yet uncharacterized Streptococcus pneumoniae ACT domain protein (pdb structure 1ZPV). Members of this CD belong to the superfamily of ACT regulatory domains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307615087  8 KAIMTVTGLDHTGIIAAVSQTLASQRVNIVNVSQTLMDEYFTMIMLLEFDPEVVSLRALQDAMKSVETAERLEIRVQAEA 87
Cdd:cd04872   1 KAVITVVGKDRVGIVAGVSTKLAELNVNILDISQTIMDGYFTMIMIVDISESNLDFAELQEELEELGKELGVKIRIQHED 80

                ....*...
gi 307615087 88 IFNTMHSL 95
Cdd:cd04872  81 IFKAMHRI 88

Glycine cleavage system regulator GcvR [Amino acid transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307615087   6 MKKAIMTVTGLDHTGIIAAVSQTLASQRVNIVNVSQTLMDEYFTMIMLLEFDPEvvSLRALQDAMKSVetAERLEIRVQA 85
Cdd:COG2716    1 MQHLVITAIGPDRPGIVAALARAVSEHGCNILDSRMARLGGEFAGILLVSGPWD--AIAKLEAALPAL--AAELGLLVTV 76

                 .
gi 307615087  86 E 86
Cdd:COG2716   77 K 77

Glycine cleavage system regulator GcvR [Amino acid transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307615087  12 TVTGLDHTGIIAAVSQTLASQRVNIVN-VSQTLMDEY-----FTMIMLLEFdPEVVSLRALQDAMKSVETAERLEIRVQA 85
Cdd:COG2716   94 EVVGNDRPGIVAEVTQFLAERGINIEDlSTKTYPAPMsgtplFSAQITVHV-PAGLDIDALRDALEDLADELNVDISLEP 172

ACT domains are commonly involved in specifically binding an amino acid or other small ligand leading to regulation of the enzyme; Members of this CD belong to the superfamily of ACT regulatory domains. Pairs of ACT domains are commonly involved in specifically binding an amino acid or other small ligand leading to regulation of the enzyme. The ACT domain has been detected in a number of diverse proteins; some of these proteins are involved in amino acid and purine biosynthesis, phenylalanine hydroxylation, regulation of bacterial metabolism and transcription, and many remain to be characterized. ACT domain-containing enzymes involved in amino acid and purine synthesis are in many cases allosteric enzymes with complex regulation enforced by the binding of ligands. The ACT domain is commonly involved in the binding of a small regulatory molecule, such as the amino acids L-Ser and L-Phe in the case of D-3-phosphoglycerate dehydrogenase and the bifunctional chorismate mutase-prephenate dehydratase enzyme (P-protein), respectively. Aspartokinases typically consist of two C-terminal ACT domains in a tandem repeat, but the second ACT domain is inserted within the first, resulting in, what is normally the terminal beta strand of ACT2, formed from a region N-terminal of ACT1. ACT domain repeats have been shown to have nonequivalent ligand-binding sites with complex regulatory patterns such as those seen in the bifunctional enzyme, aspartokinase-homoserine dehydrogenase (ThrA). In other enzymes, such as phenylalanine hydroxylases, the ACT domain appears to function as a flexible small module providing allosteric regulation via transmission of conformational changes, these conformational changes are not necessarily initiated by regulatory ligand binding at the ACT domain itself. ACT domains are present either singularly, N- or C-terminal, or in pairs present C-terminal or between two catalytic domains. Unique to cyanobacteria are four ACT domains C-terminal to an aspartokinase domain. A few proteins are composed almost entirely of ACT domain repeats as seen in the four ACT domain protein, the ACR protein, found in higher plants; and the two ACT domain protein, the glycine cleavage system transcriptional repressor (GcvR) protein, found in some bacteria. Also seen are single ACT domain proteins similar to the Streptococcus pneumoniae ACT domain protein (uncharacterized pdb structure 1ZPV) found in both bacteria and archaea. Purportedly, the ACT domain is an evolutionarily mobile ligand binding regulatory module that has been fused to different enzymes at various times.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 307615087 12 TVTGLDHTGIIAAVSQTLASQRVNIVNVSQTLMDEYFTMIMLLEFDPEVVSLRALQ 67
Cdd:cd02116   2 TVSGPDRPGLLAKVLSVLAEAGINITSIEQRTSGDGGEADIFIVVDGDGDLEKLLE 57

ACT domain found C-terminal of the RelA/SpoT domains; ACT_RelA-SpoT: the ACT domain found C-terminal of the RelA/SpoT domains. Enzymes of the Rel/Spo family enable bacteria to survive prolonged periods of nutrient limitation by controlling guanosine-3'-diphosphate-5'-(tri)diphosphate ((p)ppGpp) production and subsequent rRNA repression (stringent response). Both the synthesis of (p)ppGpp from ATP and GDP(GTP), and its hydrolysis to GDP(GTP) and pyrophosphate, are catalyzed by Rel/Spo proteins. In Escherichia coli and its close relatives, the metabolism of (p)ppGpp is governed by two homologous proteins, RelA and SpoT. The RelA protein catalyzes (p)ppGpp synthesis in a reaction requiring its binding to ribosomes bearing codon-specified uncharged tRNA. The major role of the SpoT protein is the breakdown of (p)ppGpp by a manganese-dependent (p)ppGpp pyrophosphohydrolase activity. Although the stringent response appears to be tightly regulated by these two enzymes in E. coli, a bifunctional Rel/Spo protein has been discovered in most gram-positive organisms studied so far. These bifunctional Rel/Spo homologs (rsh) appear to modulate (p)ppGpp levels through two distinct active sites that are controlled by a reciprocal regulatory mechanism ensuring inverse coupling of opposing activities. In studies with the Streptococcus equisimilis Rel/Spo homolog, the C-terminal domain appears to be involved in this reciprocal regulation of the two opposing catalytic activities present in the N-terminal domain, ensuring that both synthesis and degradation activities are not coinduced. Members of this CD belong to the superfamily of ACT regulatory domains.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 307615087 13 VTGLDHTGIIAAVSQTLASQRVNIVNVSqtlMDEYFTMIMLLEFDPEVVSLRALQDAMKSVET 75
Cdd:cd04876   3 VEAIDRPGLLADITTVIAEEKINILSVN---TRTDDDGLATIRLTLEVRDLEHLARIMRKLRQ 62