CDD Conserved Protein Domain Family: ACT

cd04880: ACT_AAAH-PDT-like

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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.

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

1PHZ,2IQ8

Conserved Protein Domain Family
ACT_AAAH-PDT-like

1PHZ,2IQ8

Conserved Protein Domain FamilyACT_AAAH-PDT-like

Conserved Protein Domain Family
ACT_AAAH-PDT-like