1PHZ,2IQ8


Conserved Protein Domain Family
ACT_AAAH-PDT-like

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cd04880: ACT_AAAH-PDT-like 
Click on image for an interactive view with Cn3D
ACT domain of the nonheme iron-dependent, aromatic amino acid hydroxylases (AAAH)
ACT domain of the nonheme iron-dependent, aromatic amino acid hydroxylases (AAAH): Phenylalanine hydroxylases (PAH), tyrosine hydroxylases (TH) and tryptophan hydroxylases (TPH), both peripheral (TPH1) and neuronal (TPH2) enzymes. This family of enzymes shares a common catalytic mechanism, in which dioxygen is used by an active site containing a single, reduced iron atom to hydroxylate an unactivated aromatic substrate, concomitant with a two-electron oxidation of tetrahydropterin (BH4) cofactor to its quinonoid dihydropterin form. Eukaryotic AAAHs have an N-terminal ACT (regulatory) domain, a middle catalytic domain and a C-terminal domain which is responsible for the oligomeric state of the enzyme forming a domain-swapped tetrameric coiled-coil. The PAH, TH, and TPH enzymes contain highly conserved catalytic domains but distinct N-terminal ACT domains and differ in their mechanisms of regulation. One commonality is that all three eukaryotic enzymes appear to be regulated, in part, by the phosphorylation of serine residues N-terminal of the ACT domain. Also included in this CD are the C-terminal ACT domains of the bifunctional chorismate mutase-prephenate dehydratase (CM-PDT) enzyme and the prephenate dehydratase (PDT) enzyme found in plants, fungi, bacteria, and archaea. The P-protein of Escherichia coli (CM-PDT) catalyzes the conversion of chorismate to prephenate and then the decarboxylation and dehydration to form phenylpyruvate. These are the first two steps in the biosynthesis of L-Phe and L-Tyr via the shikimate pathway in microorganisms and plants. The E. coli P-protein (CM-PDT) has three domains with an N-terminal domain with chorismate mutase activity, a middle domain with prephenate dehydratase activity, and an ACT regulatory C-terminal domain. The prephenate dehydratase enzyme has a PDT and ACT domain. The ACT domain is essential to bring about the negative allosteric regulation by L-Phe binding. L-Phe binds with positive cooperativity; with this binding, there is a shift in the protein to less active tetrameric and higher oligomeric forms from a more active dimeric form. Members of this CD belong to the superfamily of ACT regulatory domains.
Statistics
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PSSM-Id: 153152
View PSSM: cd04880
Aligned: 179 rows
Threshold Bit Score: 46.3342
Threshold Setting Gi: 433470
Created: 1-Aug-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
putative amino
Conserved site includes 8 residues -Click on image for an interactive view with Cn3D
Feature 1:putative amino acid binding site [chemical binding site]
Evidence:
  • Comment:based on sequence similarity to and mutational studies on phenylalanine hydroxylase and prephenate dehydratase

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                  ####                ####                                           
1PHZ_A     36 SLIFSLKe---eVGALAKVLRLFEenDINLTHIESRPSrlnkDEYEFFTYLDkr-tKPVLGSIIKSLRNd--iGATVHEL 109 Norway rat
BAD01049   47 PMIFSIKn---eLGNLAKVLKLFKenDIRVLHIESRKAnm-sSELEIFVDCEg--kKKMLKNVMDFMKDa---MLLTEVM 117 Hemicentrotus pulc...
NP_612080  80 SIIFTLRn---qVGNLARALQVFQelGINVLHLELSPLematNQADVLVDVEc--dQRRLDQVVKMLNRe---VASVNYT 151 fruit fly
XP_967413  51 SVIFTLKn---qVGGLVRALQAFQdlGINVNHIESRPSqladNQVDFLVDIDt--dQRKLDQLGRLLKRe---VQTMVIG 122 red flour beetle
12644139   33 CLLFSPKdsslsSGALANILAIFKkhDINLVHIESRSSlr-vPGYEFFVEADg--kSGALGKAIEDVKEq---CSYFNII 106 fruit fly
6226669    31 TIVFTLRe---kAGALAETLKLFQahDVNLSHIESRPSktheGCYEVLVEFAeaedHRKIEGVIEHFQQkaekKVLVQDW 107 Caenorhabditis ele...
AAD31643   31 TIVFTLRe---kAGALAETLKLFQahDVNLSHIESRPSrlmkDAMRCSLNLLklktIVRLKELLSISNKklkrRFLFKTG 107 nematode
BAE66652   42 WLLFSPErd--eAGSLARFLNIFSthGVNLSHIESRSSar-rPGYEFMVECEh--gAGDFGAALEDLKKn---VGYLNII 113 Papilio xuthus
XP_392163  24 CLIFSPKee-dsVGALARYLKLFTeyEVNLLHIESRSSlrqpNVYEFMVECAp---DGDLGSVIEKLREq---CSYFSII 96  honey bee
XP_967025  46 CLVFAPLae--eVGVLAKCLNIFKqhGVNLLHIESRPSarirNNYEFMVECAp---TGDLASAIAEIKKn---TEYFNII 117 red flour beetle
Feature 1      
1PHZ_A    110 S 110 Norway rat
BAD01049  118 T 118 Hemicentrotus pulcherrimus
NP_612080 152 S 152 fruit fly
XP_967413 123 T 123 red flour beetle
12644139  107 S 107 fruit fly
6226669   108 N 108 Caenorhabditis elegans
AAD31643  108 T 108 nematode
BAE66652  114 S 114 Papilio xuthus
XP_392163  97 S 97  honey bee
XP_967025 118 S 118 red flour beetle

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