Conserved Protein Domain Family
M1_LTA4H

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cd09599: M1_LTA4H 
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Peptidase M1 family contains leukotriene A4 hydrolase
This family includes leukotriene A4 hydrolase (LTA4H; E.C. 3.3.2.6) and the close homolog cold-active aminopeptidase (Colwellia psychrerythraea-type peptidase; ColAP), both members of the aminopeptidase M1 family. LTA4H, is a bifunctional enzyme possessing an aminopeptidase as well as an epoxide hydrolase activity. The two activities occupy different, but overlapping sites. The activity and physiological relevance of the aminopeptidase is as yet unknown while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals. It accepts a variety of substrates, including some opioid, di- and tripeptides, as well as chromogenic aminoacyl-p-nitroanilide derivatives. The aminopeptidase activity of LTA4H is possibly involved in the processing of peptides related to inflammation and host defense. Kinetic analysis shows that LTA4H hydrolyzes arginyl tripeptides with high efficiency and specificity, indicating its function as an arginyl aminopeptidase. LTA4H is overexpressed in certain human cancers, and has been identified as a functionally important target for mediating anticancer properties of resveratrol, a well known red wine polyphenolic compound with cancer chemopreventive activity.
BioAssay Targets and Results
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CID: 3017356
AID: 445449
GI: 126353
IC50: 0.0014µM
more
Inhibition of human recombinant LTA4H hydrolysis assessed as inhibition of LTB4 formation by LC-MS/MS
Target Name: Leukotriene A-4 hydrolase
Chemical Name: AC1MI4LW
IC50: 0.0014µM
CID: 46888240
AID: 480991
GI: 126353
IC50: 0.001µM
more
Inhibition of human LTA4H hydrolysis assessed as inhibition of Ca2+ ionophore-stimulated LTB4 formation in human whole blood by ELISA
Target Name: Leukotriene A-4 hydrolase
Chemical Name: CHEMBL1098531
IC50: 0.001µM
CID: 9909236
AID: 594263
GI: 126353
IC50: 0.0005µM
more
Inhibition of human leukotriene A4 hydrolase
Target Name: Leukotriene A-4 hydrolase
Chemical Name: SureCN2107334
IC50: 0.0005µM
Statistics
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PSSM-Id: 189006
View PSSM: cd09599
Aligned: 73 rows
Threshold Bit Score: 568.308
Threshold Setting Gi: 47216490
Created: 14-Sep-2010
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
Hierarchy
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Display:
 
active siteZn binding site
Conserved site includes 17 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:Bestatin is a competitive inhibitor
  • Structure:1HS6: Homo sapiens leukotriene A4 hydrolase bound to bestatin; contacts at 4.0A
    View structure with Cn3D

cd09599 is part of a hierarchy of related CD models.
Use the graphical representation to navigate this hierarchy.
cd09599 is a member of the superfamily cl14813.
cd02699:M4_M36cd06258:M3_likecd06455:M3A_TOPcd06456:M3A_DCPcd06457:M3A_MIPcd06459:M3B_PepFcd06460:M32_Taqcd06461:M2_ACEcd08662:M13cd09594:GluZincincd09595:M1cd09596:M36cd09597:M4_TLPcd09598:M4_likecd09599:M1_LTA4Hcd09600:M1_APNcd09601:M1_APN-Q_likecd09602:M1_APNcd09603:M1_APN_likecd09604:M1_APN_likecd09605:M3Acd09606:M3B_PepFcd09607:M3B_PepFcd09608:M3B_PepFcd09609:M3B_PepFcd09610:M3B_PepFcd09839:M1_like_TAF23CIA A12059851121232914243731311240034951637565132555323391491856342544177331499182671524064529446022930276179010875708720137480148227184575265402608113194721649011959160130111830211837948211837948414548347911840008811840009214548855914549195314550288714553634714554281919075633505548171720474662235900772388785452235900761904090372545685747469457574628780172052502189210201296416898302880224710032731341124233026974512264667001HS6 A3FH5 A2R59 A57525373148234122148725394260814159156362046196003128198431946245850629108695515653882511405159817544504719843532211323092191218292240100043010985153032707951617889942909746332949331973CIA A12059851121232914243731311240034951637565132555323391491856342544177331499182671524064529446022930276179010875708720137480148227184575265402608113194721649011959160130111830211837948211837948414548347911840008811840009214548855914549195314550288714553634714554281919075633505548171720474662235900772388785452235900761904090372545685747469457574628780172052502189210201296416898302880224710032731341124233026974512264667001HS6 A3FH5 A2R59 A5752537314823412214872539426081415915636204619600312819843194624585062910869551565388251140515981754450471984353221132309219121829224010004301098515303270795161788994290974633294933197
cd09599 Sequence Cluster
cd09599 Sequence Cluster
Sub-family Hierarchy
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 cd09599 Branch
 Whole Hierarchy
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CD Hierarchy
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
3CIA_A        16 DAYTYANydqVKATHVYLDLNVDFdkkSLSGFAELSLDWftdnKAPLILDTRDLVIHRVMAKnsqgqwvKVNYDLakrd- 94
gi 118379482  16 DISSLANidsVVCTHHDINLTIEFdnkRLSGSITYHLKVlq-nTSEVDLDIRNIHVSRAVLDn-----tELSFKVvqyek 89
gi 118379484  57 DELSLSNidkVKCLHYDLILYISFdkkSIEGSVNYHFEAtq-kTRKVYLDIRNIKIKNIIMDg-----qKLEYTIlsidk 130
gi 145483479  65 DKCSLSNleeVVTLNTSIKIEIDFkqqQLIGSVTLKMKAik-dINKVLLDAKLLNVQQVSVNn-----eDTQFNYkqlv- 137
gi 118400088  37 DDSTLSNildVQTKHFHLEIEIDFeskSIFGNQTLSMVAqksgVKQINLDVSNLQIYKVVDQeg----nILNFNYfnpi- 111
gi 118400092  42 DQTSYSNlleIKTTHFHLDIQLDFslnQINGTQTLFMTAtrsgASHLDLDIDGIQVQQVREEsq----gELKFVVnypk- 116
gi 145488559  18 DVNTFSNyldVQNKHIHFELLSNMekkQINATANYKFHVarssINKICLDIKELNIYSIYMEng----lLLRHIIdnpya 93
gi 145491953  20 DVNTFSNyheIQIHKLHIEWLLDLnqkIINGTAEYHFNViknnIKEIHLDIYQLDIMIAYDQat---gtVLKHEVenmge 96
gi 145502887  10 DPNTFSNyldVRMNHLHVEWLLDLdkkIVNGTAQISFKFlk-hTNYIDLDVYQLSILNVYLVng----nTLKHEIqvvke 84
gi 145536347  17 DVNTFSNyieVSQEHVHIEWLLDLdeqYINATSQSIFRVntnkLKKIDLDIYQLSIIAVYLSss---gnVLQHEIinkgd 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
3CIA_A        95 --dvlGSKLTINtp-----lnAKKVRVYYNSTek----atGLQWLSAEQTagk--------------------------- 136
gi 118379482  90 ithtlGDQLKIQlttpleagkTAQLTVEFYTLesk---esALNWLLPSQTqgk--------------------------- 139
gi 118379484 131 -tksfGEQLQIFlpqkyeqgsKFELTIQYETIqsk---hsGLNWLNPSQTegk--------------------------- 179
gi 145483479 138 -vndlGDQLEIItqkq--aneEFQIEITFSTQqnvqneqvAMNWLLPSQTfgc--------------------------- 187
gi 118400088 112 -pnifGEQLQIFlknptiegrVYNYTITYKSEna-----sASSWLTPKQTssq--------------------------- 158
gi 118400092 117 -evvtGEQLSISlkeplikgkQYIFYIDYSVQns-----sASSWLTPQQTaskilpqflleslvsgfntkqklkindnkq 190
gi 145488559  94 -dsdqGQRLNILlnreyrrgeIIMLSIKYSIDsr----seSVSFMNVSQTstk--------------------------- 141
gi 145491953  97 qslkqGDRLKIYlpksynngdQVKLRIKYGVTdk----arALSFMTKEQTesk--------------------------- 145
gi 145502887  85 qsliqGDRLHIVldrdynpleNIILKIKYAYDer----arAVGFLTKEQThsk--------------------------- 133
gi 145536347  94 qsllqGDVLSIQldrvytrgeYIKLNIKYNLDskg---arALGFLTKEQTysk--------------------------- 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                  # ##                                                                  
3CIA_A       137 ---ekPFLFSQNQAIHARSWIPIQDTPSVRVTYTARITTdk-dLLAVMSAnn--------ePGTEr----------dGDY 194
gi 118379482 140 ---qhPYLFTQCEPIWNRTIFPCQDTPAIKSTFTAHLTVpk-aFKAYASGrlv-----gqkETSEt-----------NVM 199
gi 118379484 180 ---vhPYLFTQSEPYWNRTIFPCQDSPAIKSTYTAQLHVtq-pLKAYCSAkl--------iSKSEte--------heTIM 239
gi 145483479 188 ---khPFLFTQSEPIYARSLFPCQDSPSMKSTFDIQLIVpa-pLKAYGSGliv-----ketNQGDk-----------NIF 247
gi 118400088 159 ---vlPYLYTQCQSVYCRSLAPFQDTPFIKATYTANVTVvd-pIVVYLSAnvtqs--tqvqKDNQn----------yTIY 222
gi 118400092 191 lfknnSYLFTQCESTYCRSLAPFQDSPYIKSTYSANVTVqd-pINIFLSAn----------LTSKiphpt---lkdySIY 256
gi 145488559 142 ---smPFLFTQCEDAYCRSLAPLQDTPAIKQTYSATIITriqkQQMFLQQfk-------iqNHPEidpn-----ftwKYK 206
gi 145491953 146 ---vlPYLYSYCQDNNCRSMIPLQDTPSIKQYFSALILVkdprIKVYMTGn---------lLDGRpfkrmnsyseslTEY 213
gi 145502887 134 ---kvPYMFTQCETNNCRSIIPLQDTPSVKFTFTATVIStnplIKAFMTGeqia----slpLIGQygle-----stfYTY 201
gi 145536347 144 ---avPYLFSQCEDNNCRSIIPLQDTPSIKVFFTATVLVkdprINVFMTGnklyntkfkllNNYEnlq-------alTLY 213
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
3CIA_A       195 FFSMPQAIPPYLIAIGVGDLEFKAMS----HQTGIYAESyilDAAVAEFDDTQAMIDKAEqMYGKYRWGRYDLLMLPPSF 270
gi 118379482 200 TFQQDIPIPSYLFAVVAGNLVEKKIS----DRTSVIAEPeviDKCVKELEDMEVQLKALEdFITPYDWKEYKVVVLPPSF 275
gi 118379484 240 NFKQDIPIPSYLFALVAGNLEERKTS----DRTSVISEPeviEKYTKELEDMEVQLKTLEeIITPYEWEEYKIVVLPASF 315
gi 145483479 248 QFNQPVAIPAYLFAICAGDLEKKQIS----ERTFVISEPiiiNKCSYEFSDMEKYLSTIEdYLTPYKWNQYTVVVLPKAF 323
gi 118400088 223 SFRSDIPIASYVFTIVAGNVVERKIG----RRTSVISEPtniDFYAQELSDLELYLDTVEnYTIPYIWGSYKIVIQPPSF 298
gi 118400092 257 SFRMDIPIPSYLFTIVAGNVVLQMIG----ERTGVISEPthiQAYANELSDLELYLQTLEnYTIPYTWGNYQIVILPPSF 332
gi 145488559 207 YFLQKIPIPSYLIAIVAGNLQKVPTSn--gDRTFLISEPdkiNEYKEELKDMEQFLQAIEqYIGPYTWGTYTIVILPPSF 284
gi 145491953 214 HISLDIKIPSYLLAIVAGNLEQRKVGnqqtSRSYVITEPtsiDKVAKELEFLQDYVDALAnYIGPYEWGDYKIVILPPSF 293
gi 145502887 202 SFQLNIPIPAYLIGIVAGEIEQKHIG----ANCYVISEPfylDDYAKELDELPFFIEKMTdYIGPYIWGDYKIVILPQSF 277
gi 145536347 214 QFELDIKIPAYLIGIIAGEVVEKSTG----NGTYVIAEPhfiDEYAQELSDLPVYMKKMQdYIGPYIWGDYKIVILPASF 289
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         #####                    #  ##  #              #   #      #                    
3CIA_A       271 PFGGMENPRLSFITPTVVAGDKSLVNLIAHELAHSWSGNLVTNESWrDLWLNEGFTSYVENRIMEAVfg-tDRAVMEQAL 349
gi 118379482 276 PYGGMENPLLTFASPSIIVGDKSSTDVIIHEMAHSWSGNLFSCKNWnSFWLNEGWTVYFECEIVRRLhg-eEAYKTKFTL 354
gi 118379484 316 PYGGMENPLLTFASPSIIVGDKSATDVVIHEMAHSWSGNLFTCKNWrEVWLNEGWTGYFECEAIRKLhg-eEEYQVKFSM 394
gi 145483479 324 PFGGMENPNLTFLSPSLIVGDKSEASVVIHEMIHSWSGNNMTCQNWeCFWLNEGITTFIENKMVGKIfg-kDQQTLHGLL 402
gi 118400088 299 PMGGMENPLLTFASPSIIVGDKSGVSVAVHEIAHSWTGNQVTCKNWrNLWINEGFTMYLERQSDSIMfg-kDYAVVDAIV 377
gi 118400092 333 PFGGMENPLVTFASPSIIVGDKSGVQVAIHEIAHSWFGNLVTLLNWrNVWINEGLTVYLERQANLILgg-eDNYLIDSYV 411
gi 145488559 285 PYGAMENPLLTFASPTIMTKTGSGLYVAIHEMAHSWFGNTVTCVNWgNMWINEGFTVFLERKASSFYykvpDDIKLKAII 364
gi 145491953 294 PLGGMEHPLLTFASPTIIVGDKSGVGVAIHEIGHSWVGNTVTCSDWaNMWINEGFCTFLERKILEQYng-eDYSKMYSFL 372
gi 145502887 278 PFGGMEHPLLTFASPVIIVGDKSGVGTAVHEIAHSWMGNTVTGNNWsNMWIMEGFCVFLERKTYKYVrp-qDYDIIEAIN 356
gi 145536347 290 PFGGMEHPLLTFASPTIIVGDKSGVGTAIHEIAHSWVGNTVTGRNWaNFWINEGFCVFLERKILSRLng-lDSVKLDAIN 368
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                             #    #                                     
3CIA_A       350 GAQDLNAEilelda------sdtqlYIDLKGrdpDDAFSGvPYVKGQLFLMYLEEkfGRERFDAFVLEYFDSHafqslgT 423
gi 118379482 355 LNNDLTNCidgigld----hsyttlNPQIGYdnpDDAFSTvPYVRGAQLLTHIQDvvGNEAFQKFTKSFVNTYkfksldT 430
gi 118379484 395 LDNELKNSidkighhh--syttlnpIIDLSNp--DESFVGvPYLRGLQFLTHLQNflGKNEFSKFTRSFIEKFkyksvdT 470
gi 145483479 403 GDNDLQKSissfgat----htytslSPKINQqnpDDCFSSiPYEKGCQYLRLLESqiGEVKFQEFIRLIVSQNtl---nS 475
gi 118400088 378 GNDTMVDDmnnfgmq----snytslNPMIQGsnpDDAFSNiPYEKGYQFLKYIESviGQDLLQQFLRSYISEYslksidY 453
gi 118400092 412 GNNTLMDDmngygln----snytslHPFVKGtnpDDSFSNvPYEKGFQFVAYLETvvGKEFLQGFLRSYLQKFkyqsidH 487
gi 145488559 365 GNASMYADilnfgpd----snftslHPDTTGinpQLSISDiLYEKGFQFLTFLEGiiGEEDFKYMLRSYLATYmyksidQ 440
gi 145491953 373 SNDTMFQQmarygmd----hsysslHPNTSGenpDDSQSEvPYNKGYQLLLYIEQqlGKQNFQKMLQQYIIQFkwqsidE 448
gi 145502887 357 GNFNLISAiqgltdpdeksyqtlhpITSWKNp--DDSTSSvPYERGYQLLYYLEQliGEENFKFMLRQYLDHFkfqsidE 434
gi 145536347 369 GNSSAFTSmqtfgld----nsfssmHPNTTNrnpDESTSRvPYEKGYQLLTYLESliKEDPFQQFLRDYIENFkfqsidE 444
                        490       500       510
                 ....*....|....*....|....*....|....*
Feature 1                                           
3CIA_A       424 DNFVKYLKAnltd------kypNIVSDNEINEWIF 452
gi 118379482 431 AEFLQFFKDhf---------gnEIYEKIDWESWIN 456
gi 118379484 471 QDFKESFKEff---------geQIYTQIDWNAWIT 496
gi 145483479 476 DQFRTLLKRfll-------ennIQGVDLQWQQWIV 503
gi 118400088 454 EELQAFFNKfikinr--qrdakKLLSQIDWDTWIN 486
gi 118400092 488 VTFREFFTEylilnn--prkasKILTQINWDAWIN 520
gi 145488559 441 QELQNFIIRylyeqhvdnystkRYQILEYWDSWIY 475
gi 145491953 449 DVFYRYLLSwistnl-gkdhasIKEIKTVYKEWVY 482
gi 145502887 435 DDFYKFLLDwvrsnvkvntqkiIDDIVAVYKPWVY 469
gi 145536347 445 DQLYQFLLSwvrknkqeeaqriIEEIQKIWKKWVY 479

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