1SQI,1SP9,3ISQ,1T47,2R5V,1CJX,3ZGJ,5EC3,1SQD,5CTO,1SP8


Conserved Protein Domain Family
HPPD_C_like

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cd07250: HPPD_C_like 
Click on image for an interactive view with Cn3D
C-terminal domain of 4-hydroxyphenylpyruvate dioxygenase (HppD) and hydroxymandelate synthase (HmaS)
HppD and HmaS are non-heme iron-dependent dioxygenases, which modify a common substrate, 4-hydroxyphenylpyruvate (HPP), but yield different products. HPPD catalyzes the second reaction in tyrosine catabolism, the conversion of 4-hydroxyphenylpyruvate to homogentisate (2,5-dihydroxyphenylacetic acid, HG). HmaS converts HPP to 4-hydroxymandelate, a committed step in the formation of hydroxyphenylglycerine, a structural component of nonproteinogenic macrocyclic peptide antibiotics, such as vancomycin. If the emphasis is on catalytic chemistry, HPPD and HmaS are classified as members of a large family of alpha-keto acid dependent mononuclear non-heme iron oxygenases most of which require Fe(II), molecular oxygen, and an alpha-keto acid (typically alpha-ketoglutarate) to either oxygenate or oxidize a third substrate. Both enzymes are exceptions in that they require two, instead of three, substrates, do not use alpha-ketoglutarate, and incorporate both atoms of dioxygen into the aromatic product. Both HPPD and HmaS exhibit duplicate beta barrel topology in their N- and C-terminal domains which share sequence similarity, suggestive of a gene duplication. Each protein has only one catalytic site located in at the C-terminal domain. This HPPD_C_like domain represents the C-terminal domain.
Statistics
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PSSM-Id: 319913
View PSSM: cd07250
Aligned: 52 rows
Threshold Bit Score: 198.163
Threshold Setting Gi: 19551667
Created: 17-Feb-2009
Updated: 18-Aug-2016
Structure
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Program:
Drawing:
Aligned Rows:
 
active siteFe binding site
Conserved site includes 11 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Structure:1SQI_A; active site of Rattus norvegicus 4- hydroxyphenylpyruvate dioxygenases bound to Fe(II) and inhibitor NTBC defined by 3.5 A contacts.
    View structure with Cn3D
  • Structure:2R5V_A; active site of hydroxymandelate synthase from Amycolatopsis orientalis, by 4A distance.
    View structure with Cn3D
  • Structure:1T47_A; active site of (4-hydroxyphenyl)pyruvate, by 4A distance.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1             #                                                                         #
1SQI_A       178 LEIIDHIVGNQPdqEMESASEWYLKNlQFHRFWSVddtqv-------------------------------hteysSLRS 226
gi 260831031 186 LSHFDHVTYACPmsSSPPILEWYERClGLKRFLVNrdesedqg-------------------------fivqgadvGMRL 240
gi 196009153 156 VTHIDHVTCICHqnTTVPLLNWYQKCfNFSRFTINadeeedg----------------------------ytlndlHIKM 207
gi 198422279 168 MTAVDHIAFALKleHTDEVVQWYNHClGFSRMIINieedfddg-------------------------fvvkegtrGLRL 222
gi 281211380 468 SIHMDHVATCVKngQLEKCIDWYSRCmGFNLLEVEagknkkedsrvaqlidehsrskqhkvvesqnyfnikveediGLKM 547
gi 27376164  429 LLAVDHIAQSMPydEMLSWLLFYTGIlDLKRLPQMeiad----------------------------------prgLVQS 474
gi 83744141  439 LKRIEHMAMALPadNLDRWVLFYKSLlDFTADDEVvlpd----------------------------------pygLVKS 484
gi 19551667  427 IEAIDHVNFAQPwqHFDEAVLFYTALmALETVREDefps----------------------------------pigLVRN 472
gi 214045783 433 LERIDHLAQTMSydEMLSWSLFYTTLfQMQKSPMVdvvd----------------------------------pdgLVRS 478
gi 74857714  227 TGSLDHIATCIKngEMNYFVEWYRKClGFKLLSDKdsvatdesenfenelildk----nfyvitksdfkytkkeniGLKM 302
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                              # #                      #              #                 
1SQI_A       227 IVVANye----------esIKMPINEPapg-------------rkkSQIQEYVDynggAGVQHIALRTEDIITTIRHLRE 283
gi 260831031 241 KAFEYwkca-------kegLRMPGSSPdvkpkvkfviaeplpgqgpNQVETFLEqhggPGIQHIGLHTPDIISSTRQLRA 313
gi 196009153 208 IAAQYwlcteqgiqssngrFKFLLAEPldi-------------svnNHVNGFLKeqegSGIQHIALHTENITNTVGQMKA 274
gi 198422279 223 KAVLGpqhl------eeqkLKNKVPQVpkfvlce-----alqldkkSLMEDFFSmhqgEGVQHIAFSTNNIVDAISHYKA 291
gi 281211380 548 VVLSNqpvssv--nlttppIMWVISEAavd--------------gkGQVEQFVKfnggSGIQHLAFYTDNIFEAVDYARR 611
gi 27376164  475 QAVINgd----------qsLRFVLNGSsa---------------nrTLPARFISeffgSGVQHVAFACRDIFAAVAAMRA 529
gi 83744141  485 RALRSrc----------stIRLPLNISen---------------rkTAISHALSsyggSGVHHIAFDCDDIFAEVSRAKE 539
gi 19551667  473 QVMRSpn----------daVRLLLSVApe----------------dGEQGDFLNa---AYPEHIALATADIVAVAERARK 523
gi 214045783 479 QALETad----------gsFRITLNGAet---------------hrTMAGNFLAdsfgASVQHIALSTSDIFATADAMAQ 533
gi 74857714  303 AVLSNqplnts--fhktppIQFVISEAiqg--------------geGQIEQFIHyfggEGVQHLAFNSNNIFKAVEIAKS 366
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1SQI_A       284 RGmeFLAvPSSYYRLLRenlkts---kiqvkeNMDVLEE----LKILVDYde---------------------------- 328
gi 260831031 314 AHvqLLKpPDTYYSEIGklsei-----nqvgqCLTALRE----NGVLLDAeadatdn------------------dtrnn 366
gi 196009153 275 AGtaFVTpPDTYYNNLKqadih-----etvklSAEDLKE----NNVLLDFeldkcenegh------------nsngqrrp 333
gi 198422279 292 SGlqCVLpPDAYYTENFsrnei-----edlnlTVETLKA----NNILLERnqgeaesgsdwcelnfgvsgleeqkqhlkn 362
gi 281211380 612 HLleFIEaPDYYYQNLSkreeldtvlpllskeTINDLYE----YKVLIDSdys--------------------------t 661
gi 27376164  530 RGagFLDiPDNYYDDIEakyd-------lapdLMAQLRA----NHILYDReg---------------------------- 570
gi 83744141  540 AGvpLLDiPLNYYDDLAarfd-------fddeFLSELAY----YNVLYDRda---------------------------- 580
gi 19551667  524 RGldFLPvPENYYDDVQarfd-------lpqeFLDTLKE----NHLLYDRde---------------------------- 564
gi 214045783 534 RGfkPLPmSENYYADLVarfd-------ldpdMLAALKA----ANILYDEda---------------------------- 574
gi 74857714  367 QKleFVYiPQSYYSKLDerlkh-----lfpnsIPKILKEnlmkFGILIDSdaitntnennsnnnn---nndsqnnteinq 438
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
Feature 1                #             #          #   ##         
1SQI_A       329 -kGYLLQIFTKPMqd-rPTLFLEVIQRh-nHQGFGAGNFNSLFKAFEE 373
gi 260831031 367 nqRYLMQVFTKPIfd-eDTFFLEIIQRc-gATGFGAGNITALWRSVQA 412
gi 196009153 334 daKYLLQAFTRPLldkkRSFFMEVIQRf-gARGFGGSNIRKSFTAMED 380
gi 198422279 363 tnWFIMQAFTNPVfe-eKTLFFELIQRfqtISGFGAGNIGASWRAAQK 409
gi 281211380 662 tkEKNDHYILQSIcd-tPTFFFEMIKRs-gAVGFGKGNIKALFEAVEM 707
gi 27376164  571 -dGEFFQVYTHIFd---ERFFFEIVERr-nYQGFGAANAGIRLAAQSR 613
gi 83744141  581 qgGELFHVYTEPFe---GRFFFEIIQRkngYVGYGAANVAVRLAAMAK 625
gi 19551667  565 -nGEFLHFYTRTL----GTLFFEVVERrggFAGWGETNAPVRLAAQYR 607
gi 214045783 575 -qGAFFQFYSQPYa---GGMFFEIVERrggYKGYGAPNAPFRIAAQKR 618
gi 74857714  439 niGYIKQIFTKYInd-rPTMFFELIERs-nALGFGKGNIIALFESLEK 484

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