1GK2,1GKM,1W27,1T6P


Conserved Protein Domain Family
PAL-HAL

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cd00332: PAL-HAL 
Click on image for an interactive view with Cn3D
Phenylalanine ammonia-lyase (PAL) and histidine ammonia-lyase (HAL)
PAL and HAL are members of the Lyase class I_like superfamily of enzymes that, catalyze similar beta-elimination reactions and are active as homotetramers. The four active sites of the homotetrameric enzyme are each formed by residues from three different subunits. PAL, present in plants and fungi, catalyzes the conversion of L-phenylalanine to E-cinnamic acid. HAL, found in several bacteria and animals, catalyzes the conversion of L-histidine to E-urocanic acid. Both PAL and HAL contain the cofactor 3, 5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) which is formed by autocatalytic excision/cyclization of the internal tripeptide, Ala-Ser-Gly. PAL is being explored as enzyme substitution therapy for Phenylketonuria (PKU), a disorder which involves an inability to metabolize phenylalanine. HAL failure in humans results in the disease histidinemia.
Statistics
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PSSM-Id: 176460
View PSSM: cd00332
Aligned: 86 rows
Threshold Bit Score: 322.157
Threshold Setting Gi: 67988143
Created: 6-Mar-2002
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
active sitestetramer
Conserved site includes 17 residues -Click on image for an interactive view with Cn3D
Feature 1:active sites [active site]
Evidence:
  • Comment:The four active sites of the homotetrameric enzyme are each formed by residues from three different subunits.
  • Structure:1GK2, Pseudomonas putida, histidine ammonia-lyase (Hal) mutant F329g homotetramer bound with sulfate ion and glycerol, contacts at 4 A
    View structure with Cn3D
  • Structure:1GKM_A, Pseudomonas putida HAL with bound inhibitor( L-cysteine), contacts at 4 A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                     ### # #                          #
1GK2_A        8 GTLTLAQLRAIHaa-pvRLQLDASaAPAIDASVACVEQiiaedrtaYGINTGFGLLASTRIash----------dlENLQ 76  Pseudomonas putida
EAN06794     25 AALSCAEVAAIAsg--eELVLSPEvRALVEASREIVDEavqrtepvYGLNTGLGHRRNERVsaa----------llQDYQ 92  Mesorhizobium sp...
EAN07046     13 GALKPEDVAAAAat-scKVLPSPQgMERADLSRSALAWaaradipiYGVNRGVGMARQVRIddyrefaaldeeersRQFN 91  Mesorhizobium sp...
YP_139758     6 YGLTVESIERVVkg--eKVTIAPEaYHRLKASRKIVLQvldsqqqiYGLNTGVGKNKDRKIpkd----------kiEEFN 73  Streptococcus th...
ZP_00508814  73 RALTIDQVLQVSre-drKVAVSNEsWARVARSHALLLSyarlgqpvYGLNRGVGLNKDQTPfsgdvia-pevralsETFN 150 Polaromonas sp. ...
NP_107503    11 KPLGVADVAEIArr-naRLMLGEEaMRRIRASRALIEHltglgkpmYGVTTGLGACVDTPLaqa----------dlIAFQ 79  Mesorhizobium lo...
NP_103248     9 AGVGVGDVATVArq-grKVEIGPEiIGRLDKARKVLDQaaasgqqiYGLNTGLGANLGTTVdg-----------daSAFQ 76  Mesorhizobium lo...
ZP_00414213  48 AHLRARDVAEAAadpavKFVLSVDaLELIGLSREVVQQaidsghrvYGLNTLLGSGRDTAVekk----------siLAYQ 117 Arthrobacter sp....
NP_718853    28 TSLTVDKLWEISks-geDVNISKEgWERIRASYKAPIDaaedgrsiYGLTVNYGALKDQRVagasven-epnrsesIKFN 105 Shewanella oneid...
EAN07050     13 KPFSFAQLASIAag-kvELTADDEaMRRVRAARRVLEDhiaaghpvYGATTGVGAMKDVSWtaa----------dqDLFN 81  Mesorhizobium sp...
Feature 1         #                                                                             
1GK2_A       77 RSLVLSHAAGIGapldddLVRLIMVLKINSLSRGFSGIRRKVIDALIALVNAEVYPHIPLKGSVGasgDLAPLAHMSLVL 156 Pseudomonas putida
EAN06794     93 PYIIRTHAGAIGaplsesDVRATMVARIVGIARGGAGVGLETLDLLVAMLNRRVHPQVPEFGSVGa-sDLCSMSAIAEVM 171 Mesorhizobium sp...
EAN07046     92 RNLLLSHCRAIGqpidrvEVRAAMIVRLNTLLAGGSGISAEAIQLLLAMVNRSLSPIVPGTGSVGv-gDLSSLSYIGAAM 170 Mesorhizobium sp...
YP_139758    74 RQLIYAHCVGIEpelsidNVRAAMLIHLNNMLKGYAGIQVAIPERLVDFLNLGVTPVVNGFGSVGe-gDIGILSYIGLGL 152 Streptococcus th...
ZP_00508814 151 RNMLLSHTVAYGplvpadVVRAAMLIRLNTALFGGTGMQPEVVRQYAEFLNQGITPVIRGQGSVGa-aDITVLPQIALAL 229 Polaromonas sp. ...
NP_107503    80 HSVPLSHSMGIGpalpteAVRALMTARISGMAAGGTGTSERVVMGLVAALNAGVHPVIPTWGSIGa-aDLAHLGHMARSL 158 Mesorhizobium lo...
NP_103248    77 RQLLEGRSGAVGetlpieTVRATMVARASMLSAGGSGLSPTVFVALVDALNAGVHPVMPSLGSIGa-gDLVLMTALARLL 155 Mesorhizobium lo...
ZP_00414213 118 VQVVRYHNSGVGvflgadEVRAVILARLVGFSRGGSGVRPETARFYVEMLNRGVVPAIPREGSVGs-aDLTHLAAVAAVA 196 Arthrobacter sp....
NP_718853   106 ERQMRIQAAGMEpflpeaESKMAMVIRLNQMAAGFTGMSVDAANAYMEYINNDVYPLIPSRGSEGa-nDLSMVTHVGLAL 184 Shewanella oneid...
EAN07050     82 FSLVHAHSFGTGetfspaVIRSAMAIRINMALNGHVGVSGELVDIYLAMMRADLVPVVRRTGSIGc-aDIGLMGQIGAVL 160 Mesorhizobium sp...
Feature 1                                      #####   #                                        
1GK2_A      157 lgegkary-kgqwlsatEALAVAGLePLTLAAKEGLALLNGTQASTAYALRGLFYAEDLYAAAIACGGLSVEA-----VL 230 Pseudomonas putida
EAN06794    172 igrgvamy-qgelmpalQALAAAGLaPVRLKPKEGLALISGNGLAIGAGALTVERARRVLRLADLAGALSLDA-----YG 245 Mesorhizobium sp...
EAN07046    171 mgvghiqiedgtvlpadEALRRASLpILRPVGRDAMALMSSNALSAGQGCLLLEAARTVLAAGNITYAMSLEA-----LN 245 Mesorhizobium sp...
YP_139758   153 mgeglvdy-egnryearEVFKRLHLkPIHFYAKDGLAVISSNAVSFSRLSLLIPKIKNLLYWFDLACSLSLEA-----LG 226 Streptococcus th...
ZP_00508814 230 mgegevfy-rgqrmasaEVLRTAGLgAIKPFAKDSLSMLSANAYGAALAAVAASDAQALLNQADVVAALSLEG-----LD 303 Polaromonas sp. ...
NP_107503   159 rgdgeaef-qgrimpsaEALALARLePLDLREKDGHAIIVANSLSTGTACLYLEDVAHLIDWALAAVALNYEA-----FR 232 Mesorhizobium lo...
NP_103248   156 igegeady-qgrrmpaaKALMMARLaPISLAPKDGLSLINASAVSAGSGALAITDALAALAQQQQAGALTMEG-----FG 229 Mesorhizobium lo...
ZP_00414213 197 igegqavavdgqllpggQALADAGLaPLELAPGEALALVSSNSYSIGVGALVLRRILRLADLADTALALSLEAtarhdGG 276 Arthrobacter sp....
NP_718853   185 mgewdvmy-qgkrrssaEVRKELGLkKYQPFGMDGISILSNSNVAEAQSITAVKKVEHLLDLSSVIIASSLEA-----LN 258 Shewanella oneid...
EAN07050    161 tgagevya-rghrmpaeLALSQAGIvPMIFAPRDSLASISTNAIAYAAAAHAIREAAGVFRMALAVGLTSAGA-----LG 234 Mesorhizobium sp...
Feature 1                                                          #  #                         
1GK2_A      231 GSRspfdaRIHEA--RGQRGQIDTAACFRdllgdssevslshknadkvQDPYSLRCQPQVMGACLTQLRQAAEVLGIEAN 308 Pseudomonas putida
EAN06794    246 GNPvpldsRVQAA--KSYPEQAETGQRLRellagsaiw-tpsptarslQDPVSFRTIPQVHGAVRRQVCEAATVVEVELN 322 Mesorhizobium sp...
EAN07046    246 GNVap--lLEIAGitRPFMHYTDILAQLRdildgsylw--rpsperylQDPLSFRTAPLMHAVCAESIDRLGKNLSVQIN 321 Mesorhizobium sp...
YP_139758   227 GNItplddLVVKA--KHHNGQNISSQHFQsalrdsyl---lnnktktvQDPLSFRNATLIHGAAYDSLSYVEEQLLLELE 301 Streptococcus th...
ZP_00508814 304 GNVapflaVTQAQ--RPFFGQSAAAHHIVsllqgsslw--qrseqrplQDPLSFRSTAQIHGAARDALAALHAQLVVQIN 379 Polaromonas sp. ...
NP_107503   233 SSLtaideQALAA--RPAFGQREIGARLRaelagsglw--qdkaarrlQDPLSYRCVPQVWGGLLNAFEQARLATEIELT 308 Mesorhizobium lo...
NP_103248   230 ANRtildpRLQMA--RPAAGQQEAAKALHdllarde-----mpapttiQDPLSIRCMPSIHGALIEAIGQAKRAVEIELN 302 Mesorhizobium lo...
ZP_00414213 277 GNLspfspAVQAA--KAVHGQSVTAAHVLrlleggwle--dperevsvQDALSFRAAPQTHGAIRWQVTALEDALEVELN 352 Arthrobacter sp....
NP_718853   259 GNVspflwHTVDT--KGWPQGHEAAESILshlkgsylw--sldskrnlQDPLSFRSSGQILAAAKEELRQAKELLNTAIN 334 Shewanella oneid...
EAN07050    235 ASRdp--wLAASQ--LDGACKAIVGAWLYdnaevwg-----wseathvQDPLSLRMMAQVFGAAFDGLVAAGRTILAATG 305 Mesorhizobium sp...
Feature 1           #                                #                                          
1GK2_A      309 AVSDNPLVFAa---------------------eGDVISGGNGHAEPVAMAADNLALAIAEIGSLSERRISLMMDKHMs-- 365 Pseudomonas putida
EAN06794    323 SRSDNPLVDVg---------------------sGAILSNGNFQALPIALAFDGLRTGICHIASMSERRCSHVFRKLQ--- 378 Mesorhizobium sp...
EAN07046    322 SIEDNPSIVTcraddvsehlr-pyfgggddhlfGGAIPTAYFDPLPWVLDIQSMAVAFAHLSNASMQRAGRLINTHFt-- 398 Mesorhizobium sp...
YP_139758   302 SSDDNPMVDId---------------------nQRILSTPHFETLNVSLAIEMLNVALSHVSNASIQRMIKLGNPDFt-- 358 Streptococcus th...
ZP_00508814 380 SSDDNPTVALdvrpatnatpqerryfvtegavqGAILPSASFDPTVWAVSLEGVGIAMSHVAQSSAQRVLRLGDPAFt-- 457 Polaromonas sp. ...
NP_107503   309 HSGDNPVILAe---------------------gERVISNGNFDLTAMTLAWEQLGQALAHCAVGTANRCMKLMSPTTa-- 365 Mesorhizobium lo...
NP_103248   303 AAADNPLVIGd---------------------dELVLSTGNFHTASLSLAFETLGLAIAQCAAASVARFIQLTGSGRn-- 359 Mesorhizobium lo...
ZP_00414213 353 GRGDNPLTDIg---------------------sGRMVSGGNFQPMQLALAFEALRLGLAHLGISSERRIAKLYPPQRrir 411 Arthrobacter sp....
NP_718853   335 HTTDNPIVHTnarddlwysnsdyvdglrvggknVFVNSGSNFDNTQLAVQLESLSRALAQVIHISAWRTTQLDDGHRt-- 412 Shewanella oneid...
EAN07050    306 RTDDNPVVVN-----------------------GRVLTSGGSLPLDVTLFLQTAQLAIAHVARNGFNRCVLLGNGGRr-- 360 Mesorhizobium sp...
Feature 1                                                                                       
1GK2_A      366 --QLPPFLve-ngGVNSGFMIAQVTAAALASENKALShphsvdslpTSANQEDHVSMAPAAGKRLWEMAENTRGVLAIEW 442 Pseudomonas putida
EAN06794    379 --AMSSIDdaiqnAEMPVTSLVAYSAAELSARLRTLAapasihvpsLAHDVEDHGSLGPGTIAFTAQSLDLLEMLLAVEI 456 Mesorhizobium sp...
EAN07046    399 --KIDMLArqptaSAFGFAKICNVLQAQIAASLQPLStlv----qpSAGDIEDVGNHAPTIVRRAAQAMDDVLRMLSVEL 472 Mesorhizobium sp...
YP_139758   359 --GLSRFLia-deHQYFGLQALQKTAATLDVEIHHASqtlsnisypLAGEMEDRQTNLPLILQELDGIVNKLHEILAIEL 435 Streptococcus th...
ZP_00508814 458 --RLSRFLsp--gGGVLAYTTIQKTVSSLSTEVRALSqpvssdslvLAGNIEDVASNAPLAAQRVAQQIKLVRTLLGIET 533 Polaromonas sp. ...
NP_107503   366 --ELPRFLsa-rgGSRQGYAELQKPLSALEAEIRHLAnpmslsplaVSDGIEDQSSMAPRVVAKTAEIVERMRYLVAMEL 442 Mesorhizobium lo...
NP_103248   360 --GLTKYLsp-igGASAGFVPLQKTATSILAAIRHKAnpvmldflpVSEGVEDHATQSPLAVSKCAGMIALWRRLIAFEL 436 Mesorhizobium lo...
ZP_00414213 412 qrHLEAATngaplEPEELPGLLWYSAAGLLSELKFLAapatlgaptLSADVEDHSTLAPLALQQLERSVDAAGKLLAIEA 491 Arthrobacter sp....
NP_718853   413 --KLTTYLiskenVGGDGFANIAQSMSGLYAEAMSLTnsaaiygvpTSVGIEETFSNVNLIANRLDKIADIAYEIYSYEV 490 Shewanella oneid...
EAN07050    361 --GLPVNLvp-hgEIATGMGPVIKLAGALFARVLSLAspvsaqimvLADGQEDEATFLPLVVERLEQQVSALRQLAALEG 437 Mesorhizobium sp...
Feature 1                 
1GK2_A      443 LGACQGLDLR 452 Pseudomonas putida
EAN06794    457 HLSAALADCA 466 Mesorhizobium sp. BNC1
EAN07046    473 VVADSLITAR 482 Mesorhizobium sp. BNC1
YP_139758   436 LYATQAIAIR 445 Streptococcus thermophilus LMG 18311
ZP_00508814 534 IHAAQAIDLR 543 Polaromonas sp. JS666
NP_107503   443 IFAATGVELR 452 Mesorhizobium loti MAFF303099
NP_103248   437 MAAAQAVDLR 446 Mesorhizobium loti MAFF303099
ZP_00414213 492 LTAAYLLGAA 501 Arthrobacter sp. FB24
NP_718853   491 LHTTQGMDIR 500 Shewanella oneidensis MR-1
EAN07050    438 VLTAQAIDIT 447 Mesorhizobium sp. BNC1

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