1F3Y,1JKN


Conserved Protein Domain Family
Ap4A_hydrolase_plant_like

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cd03671: Ap4A_hydrolase_plant_like 
Click on image for an interactive view with Cn3D
Diadenosine tetraphosphate (Ap4A) hydrolase is a member of the Nudix hydrolase superfamily. Members of this family are well represented in a variety of prokaryotic and eukaryotic organisms. Phylogenetic analysis reveals two distinct subgroups where plant enzymes fall into one group (represented by this subfamily) and fungi/animals/archaea enzymes fall into another. Bacterial enzymes are found in both subfamilies. Ap4A is a potential by-product of aminoacyl tRNA synthesis, and accumulation of Ap4A has been implicated in a range of biological events, such as DNA replication, cellular differentiation, heat shock, metabolic stress, and apoptosis. Ap4A hydrolase cleaves Ap4A asymmetrically into ATP and AMP. It is important in the invasive properties of bacteria and thus presents a potential target for the inhibition of such invasive bacteria. Besides the signature nudix motif (G[X5]E[X7]REUXEEXGU where U is Ile, Leu, or Val), Ap4A hydrolase is structurally similar to the other members of the nudix superfamily with some degree of variations. Several regions in the sequences are poorly defined and substrate and metal binding sites are only predicted based on kinetic studies.
Statistics
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PSSM-Id: 239643
View PSSM: cd03671
Aligned: 41 rows
Threshold Bit Score: 137.337
Threshold Setting Gi: 68128542
Created: 5-Feb-2006
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 15 residues -Click on image for an interactive view with Cn3D
Feature 1:Ap4A binding site [chemical binding site]
Evidence:
  • Structure:1JKN_A; L. angustifolius Ap4A binds ATP-MgFx, a substrate analog; defined at 3.5A contacts.
    View structure with Cn3D
  • Comment:Ap4A (ATP +AMP) is the preferred substrate, although Ap4A hydrolase also hydrolyzes Ap4 (ATP + P), Ap5A (ATP +ADP), Ap6A (2x ATP), and Ap4N (ATP + NMP, where N is any nucleoside).

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1         #                #  #        #  ##                                          
1F3Y_A     12 GYRRNVGICLMNndkKIFAASRLDIp----dAWQMPQGGIDEG--EDPRNAAIRELREETGVt----------------- 68  narrow-leaved blue...
1JKN_A     12 GYRRNVGICLMNndkKIFAASRLDIp----dAWQMPQGGIDEG--EDPRNAAIRELREETGVt----------------- 68  narrow-leaved blue...
AAN51175    4 PYRKNVGMVVFNsrgEVLVGERLNFl----gSWQFPQGGIDDD--EDPIKAAMRELYEEVGId----------------- 60  Leptospira interro...
AAX80585    1 MYRKNVCVVIFNedlNFLACQRIHEd-----KFQFVQGGVEEGd-ADIIRAAYREVHEEVGLfp---------------- 58  Trypanosoma brucei
AAX80970   47 KFRRSVCVFIMNengHFLGCRRYDDr----sTIQCVQGGAKRG--ETVQQTATREVMEEIGVhc---------------- 104 Trypanosoma brucei
XP_637504   5 KYRSCVGALIFNdqgQVLVCKRASKkktavgKWQFPQGGVEAGrdEDYYVAVLREIKEEVGLevt--------------- 69  Dictyostelium disc...
CAJ08674   11 AYRRSVQVFFVNeraQFLLCQPAGTsn--vkFRQTVQGGSEGD--ESPQKTAQRETWEEIGVdldkdatflcevhpsaav 86  Leishmania major
CAJ01925    1 MYRPNVCVFLFNekvEFLGCQRMKTd-----HFQCVQGGIEAYd-VDIRLAALREVEEEIRLkp---------------- 58  Leishmania major
EAN86518   40 RYRRSVCVVIMNdrgQFLGCRRCDNr----qILQFVQGGAKSH--ETVQQTAEREVFEEIGLpa---------------- 97  Trypanosoma cruzi
EAN88996    1 MYRKNVCVAIFNedlRFLGCRRIQDn-----LFQFVQGGIEKD--ADLLHAAYREVYEETSLrk---------------- 57  Trypanosoma cruzi
Feature 1                                               # #   #  ##          #                
1F3Y_A     69 -------------SAEVIAEv----------------pYWLTYDFPPKVREKLniqwgsdwkGQAQKWFLFKFtgq-dqE 118 narrow-leaved blue...
1JKN_A     69 -------------SAEVIAEv----------------pYWLTYDFPPKVREKLniqwgsdwkGQAQKWFLFKFtgq-dqE 118 narrow-leaved blue...
AAN51175   61 -------------SGKIVAEy----------------pDWISYDFPENLPLNRhlq---kyrGQLQKWFLIYWdge-vdQ 107 Leptospira interro...
AAX80585   59 ------------eDLRLIGEimpp----------sgdpHEFRYILHEGANLRHfg-----yvGQQQRLFLFYTpsstiqR 111 Trypanosoma brucei
AAX80970  105 ------------dQLQFISEityskpecgepqncdgprSAFRYKSKSWRRIGIv--------GQELYPLLYSMqs---sV 161 Trypanosoma brucei
XP_637504  70 -----------ddKLRFVSKiee------------plsYLYEYKNSITKAIGKvfn----hnGQMIHWHLFFLpkdlisL 122 Dictyostelium disc...
CAJ08674   87 sgehgqaedvrneKNEIVSEr----------------rKEFRYKSKTWRKLGIs--------GQELYPLLYLLks---eK 139 Leishmania major
CAJ01925   59 ------------qDVSFVQEippp----------hgdpMNFAYTLASNANLRRfg-----yvGQKQRILLFFTpsenisK 111 Leishmania major
EAN86518   98 ------------kHLRFVAEilpktv-------grevrAAFRYRSKTWRKKDIi--------GQELYPLLYLAea---gV 147 Trypanosoma cruzi
EAN88996   58 ------------eDLHFVGEvppp----------sgdpREFRYELRRTSNLRNfg-----fqGQEQRVLLFFTdsgnieK 110 Trypanosoma cruzi
Feature 1                                           #      ##           
1F3Y_A    119 INLLgdg----sekPEFGEWSWVTp------EQLIDLTVe-----FKKPVYKEVLSVF 161 narrow-leaved blue lupine
1JKN_A    119 INLLgdg----sekPEFGEWSWVTp------EQLIDLTVe-----FKKPVYKEVLSVF 161 narrow-leaved blue lupine
AAN51175  108 CDLDih-------eREFGTVRFIPi------KNTLNTVVp-----FKKDVYYKIVNDF 147 Leptospira interrogans serovar Lai str. ...
AAX80585  112 VRLVppkg--svakQEFSHVEWLPi------DEIIERCPk-----EKQHIFVAVSKVA 156 Trypanosoma brucei
AAX80970  162 INHLnfhsv-pgtrREFIGAEWVPl------HVLRNKCS------KSKQVAVSNMCDA 206 Trypanosoma brucei
XP_637504 123 IDLGfe------ekPEFDECKWFNfddflnqEEQPNNNDqtlpvpFKKEMYKQLLTLS 174 Dictyostelium discoideum AX4
CAJ08674  140 LRHVdtlgskrgvrTEFWSVAWGSl------ADLAEKAP------PRKRAVMRSVCNA 185 Leishmania major
CAJ01925  112 VVLIpppe--shasQEFRKVEWMPi------EQLISKSPp-----EKAHIFKTVGEVA 156 Leishmania major
EAN86518  148 VDLLhfkav-pgvrQEFCEAKWMTl------EELMQNCP------PSKAAVMANICMA 192 Trypanosoma cruzi
EAN88996  111 VNVIppke--tcaqQEFSQVHWMEl------REIIDRCPr-----EKLHIFLAVAKVG 155 Trypanosoma cruzi

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