2WK1


Conserved Protein Domain Family
TylF

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pfam05711: TylF 
Macrocin-O-methyltransferase (TylF)
This family consists of bacterial macrocin O-methyltransferase (TylF) proteins. TylF is responsible for the methylation of macrocin to produce tylosin. Tylosin is a macrolide antibiotic used in veterinary medicine to treat infections caused by Gram-positive bacteria and as an animal growth promoter in the swine industry. It is produced by several Streptomyces species. As with other macrolides, the antibiotic activity of tylosin is due to the inhibition of protein biosynthesis by a mechanism that involves the binding of tylosin to the ribosome, preventing the formation of the mRNA-aminoacyl-tRNA-ribosome complex. The structure of one representative sequence from this family, NovP, shows it to be an S-adenosyl-l-methionine-dependent O-methyltransferase that catalyzes the penultimate step in the biosynthesis of the aminocoumarin antibiotic novobiocin. Specifically, it methylates at 4-OH of the noviose moiety, and the resultant methoxy group is important for the potency of the mature antibiotic. It is likely that the key structural features of NovP are common to the rest of the family and include: a helical 'lid' region that gates access to the co-substrate binding pocket and an active centre that contains a 3-Asp putative metal binding site. A further conserved Asp probably acts as the general base that initiates the reaction by de-protonating the 4-OH group of the noviose unit.
Statistics
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PSSM-Id: 399021
Aligned: 16 rows
Threshold Bit Score: 350.075
Threshold Setting Gi: 219116731
Created: 11-May-2020
Updated: 7-Aug-2020
Structure
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Program:
Drawing:
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
2WK1_A               35 SSLYLDLMIKVLAGTVYEDpa------------------------------hRENFSHRDSTYREEVRNEGRDW------ 78 
WP_015846207          6 AEMYLELLKKTILFEIWLE---------------------------------------HEPGATKENRLQGLDW------ 40  Paenibac...
jgi:FraEuI1c_5710    24 NEDYLDLMKRILTNTIYQD----------------------------------PPVSRAEAAFDGDRRATGQDW------ 63  Frankia ...
CAL99994             22 GTRYLELMKRVLTNVVYEDvth----------------------------rlDHANARGNPRFDPERRRNGLDW------ 67  Saccharo...
EST19413             11 SSLYLDLMIKVLAGTVYEDpa------------------------------hRENFSHRDSTYREEVRNEGRDW------ 54  Streptom...
jgi:Haur_2419         6 AQLYLDLLKRCIMGLVYEDqplrniv--------------------yepfsiNAPYTGPYSTFDREKRLNGHEW------ 59  Herpetos...
rhodo:RCAP_rcc02435 319 GERYLDLLKAVLLNETGLEtevaldalrgrkdip----pafwsetlydvpgqLAPALAEKR----RLRAQGLDTltaqag 390 Rhodobac...
WP_014747567          4 TRLYLDLLKQVLLNQTGLEaelrlahvaachvagtdpdpyhlrdirfteaetFAAAAARRD----DGRWTAADR------ 73  Tistrell...
jgi:Plim_3940        20 tDPYIELLKNVLTGAVYEEsawrredgyhrdkfr---plkslrqfflkswakRGYLVVKAQHFDAKKRELGTDW------ 90  Planctop...
MA:Minf_0538         10 RELYIELLKNSLTFRLYPEqlgilnflrippw-------igwalrffvkqldKRDLVLARRKTERDVEE-GNFW------ 75  Methylac...
2WK1_A               79 P--ANAHTMIGIKRLENIRQCVEDVIGNNVPGDLVETGVWRGGACILMRGILRAHDVRDRTVWVADSFQGIPDVGEdGYA 156
WP_015846207         41 P--IIAHSMIGRIRMNNLHMLMNDVIANNVQGDFIETGVWRGGACIFMAGYLKAHGVRKRKVLVADSFEGLPKPDP-QYP 117 Paenibac...
jgi:FraEuI1c_5710    64 P--SVAHTMVGRARLDNVHACAATAITEGVPGDLVETGVWRGGTAIFMRAVLRAYGATDRLVWACDSFEGMPVSGPdSHP 141 Frankia ...
CAL99994             68 P--SVAHTMIGRKRLDNLHDCLERVVADDVPGDLAETGVWRGGACIFMRAFLAAHGITDRQVWVADSFEGMPDTDGsAHD 145 Saccharo...
EST19413             55 P--ANAHTMIGIKRLENIRQCVEDVIGNNVPGDLVETGVWRGGACILMRGILRAHDVRDRTVWVADSFQGIPDVGEdGYA 132 Streptom...
jgi:Haur_2419        60 P--SQAHTMLSMHRLNNIQSLVTDILEKQIPGDLIETGVWRGGATIFMRGILKAYNCNDRTVWVADSFQGFPKNEEeGLL 137 Herpetos...
rhodo:RCAP_rcc02435 391 P--PLGYTMIGRRRLDHLQDCVATVLAEAVPGDLMECGVWRGGACLLMKAMLDLAGAQDRSLWVADSFAGLPPP---ALP 465 Rhodobac...
WP_014747567         74 PglGLAYTMTGRQRLDHLEACLDDIRTEGVPGDLIETGVWRGGCGIFMRGYLAVHAMADRRVWLADSFAGVPAP---SHA 150 Tistrell...
jgi:Plim_3940        91 P--LFGYSMVGKRRLDQLEVAIRTIAAEQIPGNILEAGVWRGGASMFMKALLNHLGEGHRQLWLADSFEGLPKP---RLA 165 Planctop...
MA:Minf_0538         76 P--LYAQTMVGLKRLRNVQECIEDVLENGIEGDFLEAGVWRGGCAIFMKGMLVAWGDTKRKVFVADSFSGFPSHKPsIFS 153 Methylac...
2WK1_A              157 GDR----------K-MALHRRNSv--L-----AVSEEEVRRNFRNYDLLDEQVRFLPGWFKDTLPTAPIDTLAVLRMDGD 218
WP_015846207        118 IDA----------T-SKFHEQDF---L-----RVSLPEVQGNFKKYDLLDDSVVFLKGWFKDTLPTAPTEKIAIARLDGD 178 Paenibac...
jgi:FraEuI1c_5710   142 SDQ----------Q-TRLHLANAv--L-----AIPLEQVRANFDVYGLLDDQVRFLKGWFRDTLPTAPIERIAVLRLDGD 203 Frankia ...
CAL99994            146 LDR----------E-LALHRMNEv--L-----GIPLEVVRDNFRRYGLLDEQVRFLPGWFADTLPAAPVSELAVLRLDGD 207 Saccharo...
EST19413            133 GDR----------K-MALHRRNSv--L-----AVSEDEVRRNFRNYDLLDEQVRFLPGWFKDTLPTAPIDTLAVLRMDGD 194 Streptom...
jgi:Haur_2419       138 GETespglpqeqhG-PPPKPIQDi--LdllwkGTSYEDVRQHFEQYGLLDDQVKFLKGWFCHTLHQAPIDNLALLRLDGD 214 Herpetos...
rhodo:RCAP_rcc02435 466 EDE----------GlDLSRERAPa--L-----AVSQARVERAFADFGLLDARVRFLPGFFADTLAGCAVEKLALLRLDGD 528 Rhodobac...
WP_014747567        151 IDA----------G-DTLFQQNDl--L-----AISRPLVEDAFRRFDLLDDRVRFVEGLFEETLPGLDTGPLALLRLDGD 212 Tistrell...
jgi:Plim_3940       166 PDT----------K-DKRHDLSEcdfL-----KVSIETVSANFERFGLLDENVRFLKGWFCDSLPHANPGKLALLRLDGD 229 Planctop...
MA:Minf_0538        154 SES----------GfDKSSy------I-----AVSEEEVRDNFRRYGLLDDRVIFIKGYFEETLIHAPVEKLDILRIDAD 212 Methylac...
2WK1_A              219 LYESTWDTLTNLYPKVSVGGYVIVDDYMMcPPCKDAVDEYRAKFDIADELITIDRDGVYWQ 279
WP_015846207        179 MYSSTMDALNNLYPKVSLGGYVIIDDYSI-GYCAAAVHDFRAAHNITDPLVTIDITGVYWK 238 Paenibacillus sp. JDR-2
jgi:FraEuI1c_5710   204 LYESTMDTLDSLYPKVSPGGFVIIDDYQI-PACREAVHDYRDAHGITAPLTRIDQWAVFWR 263 Frankia inefficax
CAL99994            208 LYESTMDALVHLYPRLSPGGFVIVDDYAL-PPCRAAVREFRRDNGIHEPVEWIDYMGVYWR 267 Saccharopolyspora erythraea...
EST19413            195 LYESTWDTLTNLYPKVSVGGYVIVDDYMMcPPCKDAVDEYRAKFDIADELITIDRDGVYWQ 255 Streptomyces niveus NCIMB 1...
jgi:Haur_2419       215 LYDSTYDALEALYPKVSQGGYVIVDDYATfEECYNAVHDYLESIGAEVTMQPIDEDSVFWQ 275 Herpetosiphon aurantiacus D...
rhodo:RCAP_rcc02435 529 LYSSTLQALEALYDRVAPGGFVIIDDYGAlGQCALAVDRFRAARGITAPLGMIDWTGAFWR 589 Rhodobacter capsulatus SB 1003
WP_014747567        213 LFTSTCAALEALYDRVAPGGWIIIDDYGAvQGCRIATDMFRHVRGITTPLDRVDWTCVAWR 273 Tistrella mobilis
jgi:Plim_3940       230 LYESTMDVLKPLYQNVVPGGFVVVDDYLAwSGCREAIDEFRELHKINAPMFNIDGTGVYWR 290 Planctopirus limnophila DSM...
MA:Minf_0538        213 LYSAYKAALNALYDKLSIGGYCIIDDYVM-EGCRAAVDEYRKEKGILAPLRQIDWTGVYWK 272 Methylacidiphilum infernoru...
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