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Protein

Narbonolide/10-deoxymethynolide synthase PikA3, module 5

Gene

pikAIII

Organism
Streptomyces venezuelae
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide.1 Publication2 Publications

Catalytic activityi

Malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH = 10-deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O.1 Publication1 Publication
Malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH = narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O.1 Publication1 Publication

Cofactori

pantetheine 4'-phosphate1 PublicationNote: Binds 1 phosphopantetheine covalently.Curated

Pathwayi: Antibiotic biosynthesis

This protein is involved in Antibiotic biosynthesis.2 Publications
View all proteins of this organism that are known to be involved in Antibiotic biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei209Acyl-thioester intermediate; for beta-ketoacyl synthase activityPROSITE-ProRule annotation1 Publication1
Active sitei655Acyl-ester intermediate; for acyltransferase activityBy similarity1
Binding sitei1226NADP (Beta-ketoacyl reductase)By similarity1
Active sitei1263Acyl-ester intermediate; for beta-ketoacyl reductase activityBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1124 – 1127NADP (Beta-ketoacyl reductase)By similarity4
Nucleotide bindingi1147 – 1150NADP (Beta-ketoacyl reductase)By similarity4
Nucleotide bindingi1176 – 1177NADP (Beta-ketoacyl reductase)By similarity2
Nucleotide bindingi1248 – 1249NADP (Beta-ketoacyl reductase)By similarity2

GO - Molecular functioni

  • cofactor binding Source: InterPro
  • phosphopantetheine binding Source: UniProtKB
  • transferase activity, transferring acyl groups other than amino-acyl groups Source: UniProtKB

GO - Biological processi

  • macrolide biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Antibiotic biosynthesis

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-18413.

Names & Taxonomyi

Protein namesi
Recommended name:
Narbonolide/10-deoxymethynolide synthase PikA3, module 5Curated (EC:2.3.1.2391 Publication1 Publication, EC:2.3.1.2401 Publication1 Publication)
Alternative name(s):
Narbonolide/10-deoxymethynolide synthase PikAIIICurated
Pikromycin polyketide synthase component PikAIII1 Publication
Short name:
Pikromycin PKS component PikAIII1 Publication
Type I modular polyketide synthase PikAIII1 Publication
Short name:
PKS1 Publication
Gene namesi
Name:pikAIII1 Publication
ORF Names:BN2537_6637Imported
OrganismiStreptomyces venezuelae
Taxonomic identifieri54571 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaStreptomycetalesStreptomycetaceaeStreptomyces

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi735E → A: Exhibits 10-fold reduced formation of the 10-deoxymethynolide macrolactone. 1 Publication1
Mutagenesisi747R → A: Exhibits 5-fold reduced formation of the 10-deoxymethynolide macrolactone. 1 Publication1
Mutagenesisi766E → R: Exhibits a reduced formation of the 10-deoxymethynolide macrolactone. 1 Publication1
Mutagenesisi768E → R: Exhibits a reduced formation of the 10-deoxymethynolide macrolactone. 1 Publication1
Mutagenesisi1133R → E: Exhibits 14-fold reduced formation of the 10-deoxymethynolide macrolactone. 1 Publication1
Mutagenesisi1137H → E: Exhibits 2-fold reduced formation of the 10-deoxymethynolide macrolactone. 1 Publication1
Mutagenesisi1308R → E: Exhibits 8-fold reduced formation of the 10-deoxymethynolide macrolactone. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004363591 – 1562Narbonolide/10-deoxymethynolide synthase PikA3, module 5Add BLAST1562

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1438O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation1 Publication1

Keywords - PTMi

Phosphopantetheine, Phosphoprotein

Interactioni

Subunit structurei

Homodimer (PubMed:19146481). Pikromycin PKS consists of a combination of multimodular (PikAI and PikAII) and monomodular (PikAIII and PikAIV) polypeptides each coding for a functional synthase subunit which participates in 1 (monomodular) or 2 (multimodular) of the six FAS-like elongation steps required for formation of the polyketide. Module 1, 2, 3, 4, 5, and 6 participating in biosynthesis steps 1, 2, 3, 4, 5, and 6, respectively.1 Publication1 Publication

Protein-protein interaction databases

DIPiDIP-61040N.

Structurei

Secondary structure

11562
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1544 – 1546Combined sources3
Helixi1549 – 1557Combined sources9
Helixi1559 – 1562Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3F5HX-ray1.75A/B1534-1562[»]
ProteinModelPortaliQ9ZGI3.
SMRiQ9ZGI3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9ZGI3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1405 – 1475Acyl carrierPROSITE-ProRule annotationAdd BLAST71

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni37 – 1475Module 5CuratedAdd BLAST1439
Regioni37 – 467Beta-ketoacyl synthaseCuratedAdd BLAST431
Regioni565 – 866AcyltransferaseCuratedAdd BLAST302
Regioni1116 – 1293Beta-ketoacyl reductaseCuratedAdd BLAST178

Sequence similaritiesi

Contains 1 acyl carrier domain.PROSITE-ProRule annotation

Phylogenomic databases

KOiK16002.

Family and domain databases

Gene3Di1.10.1200.10. 1 hit.
3.40.366.10. 2 hits.
3.40.47.10. 2 hits.
3.40.50.720. 1 hit.
InterProiIPR001227. Ac_transferase_dom.
IPR014043. Acyl_transferase.
IPR016035. Acyl_Trfase/lysoPLipase.
IPR032821. KAsynt_C_assoc.
IPR018201. Ketoacyl_synth_AS.
IPR014031. Ketoacyl_synth_C.
IPR014030. Ketoacyl_synth_N.
IPR016036. Malonyl_transacylase_ACP-bd.
IPR016040. NAD(P)-bd_dom.
IPR020801. PKS_acyl_transferase.
IPR020841. PKS_Beta-ketoAc_synthase_dom.
IPR013968. PKS_KR.
IPR020806. PKS_PP-bd.
IPR015083. Polyketide_synth_docking.
IPR009081. PP-bd_ACP.
IPR006162. Ppantetheine_attach_site.
IPR016039. Thiolase-like.
[Graphical view]
PfamiPF00698. Acyl_transf_1. 1 hit.
PF08990. Docking. 1 hit.
PF16197. KAsynt_C_assoc. 1 hit.
PF00109. ketoacyl-synt. 1 hit.
PF02801. Ketoacyl-synt_C. 1 hit.
PF08659. KR. 1 hit.
PF00550. PP-binding. 1 hit.
[Graphical view]
SMARTiSM00827. PKS_AT. 1 hit.
SM00825. PKS_KS. 1 hit.
SM00823. PKS_PP. 1 hit.
[Graphical view]
SUPFAMiSSF101173. SSF101173. 1 hit.
SSF47336. SSF47336. 1 hit.
SSF51735. SSF51735. 2 hits.
SSF52151. SSF52151. 2 hits.
SSF53901. SSF53901. 3 hits.
SSF55048. SSF55048. 1 hit.
PROSITEiPS50075. ACP_DOMAIN. 1 hit.
PS00606. B_KETOACYL_SYNTHASE. 1 hit.
PS00012. PHOSPHOPANTETHEINE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9ZGI3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANNEDKLRD YLKRVTAELQ QNTRRLREIE GRTHEPVAIV GMACRLPGGV
60 70 80 90 100
ASPEDLWQLV AGDGDAISEF PQDRGWDVEG LYDPDPDASG RTYCRSGGFL
110 120 130 140 150
HDAGEFDADF FGISPREALA MDPQQRLSLT TAWEAIESAG IDPTALKGSG
160 170 180 190 200
LGVFVGGWHT GYTSGQTTAV QSPELEGHLV SGAALGFLSG RIAYVLGTDG
210 220 230 240 250
PALTVDTACS SSLVALHLAV QALRKGECDM ALAGGVTVMP NADLFVQFSR
260 270 280 290 300
QRGLAADGRS KAFATSADGF GPAEGAGVLL VERLSDARRN GHRILAVVRG
310 320 330 340 350
SAVNQDGASN GLTAPHGPSQ QRVIRRALAD ARLAPGDVDV VEAHGTGTRL
360 370 380 390 400
GDPIEAQALI ATYGQEKSSE QPLRLGALKS NIGHTQAAAG VAGVIKMVQA
410 420 430 440 450
MRHGLLPKTL HVDEPSDQID WSAGTVELLT EAVDWPEKQD GGLRRAAVSS
460 470 480 490 500
FGISGTNAHV VLEEAPAVED SPAVEPPAGG GVVPWPVSAK TPAALDAQIG
510 520 530 540 550
QLAAYADGRT DVDPAVAARA LVDSRTAMEH RAVAVGDSRE ALRDALRMPE
560 570 580 590 600
GLVRGTSSDV GRVAFVFPGQ GTQWAGMGAE LLDSSPEFAA SMAECETALS
610 620 630 640 650
RYVDWSLEAV VRQEPGAPTL DRVDVVQPVT FAVMVSLAKV WQHHGITPQA
660 670 680 690 700
VVGHSQGEIA AAYVAGALTL DDAARVVTLR SKSIAAHLAG KGGMISLALD
710 720 730 740 750
EAAVLKRLSD FDGLSVAAVN GPTATVVSGD PTQIEELART CEADGVRARI
760 770 780 790 800
IPVDYASHSR QVEIIEKELA EVLAGLAPQA PHVPFFSTLE GTWITEPVLD
810 820 830 840 850
GTYWYRNLRH RVGFAPAVET LAVDGFTHFI EVSAHPVLTM TLPETVTGLG
860 870 880 890 900
TLRREQGGQE RLVTSLAEAW ANGLTIDWAP ILPTATGHHP ELPTYAFQTE
910 920 930 940 950
RFWLQSSAPT SAADDWRYRV EWKPLTASGQ ADLSGRWIVA VGSEPEAELL
960 970 980 990 1000
GALKAAGAEV DVLEAGADDD REALAARLTA LTTGDGFTGV VSLLDDLVPQ
1010 1020 1030 1040 1050
VAWVQALGDA GIKAPLWSVT QGAVSVGRLD TPADPDRAML WGLGRVVALE
1060 1070 1080 1090 1100
HPERWAGLVD LPAQPDAAAL AHLVTALSGA TGEDQIAIRT TGLHARRLAR
1110 1120 1130 1140 1150
APLHGRRPTR DWQPHGTVLI TGGTGALGSH AARWMAHHGA EHLLLVSRSG
1160 1170 1180 1190 1200
EQAPGATQLT AELTASGARV TIAACDVADP HAMRTLLDAI PAETPLTAVV
1210 1220 1230 1240 1250
HTAGAPGGDP LDVTGPEDIA RILGAKTSGA EVLDDLLRGT PLDAFVLYSS
1260 1270 1280 1290 1300
NAGVWGSGSQ GVYAAANAHL DALAARRRAR GETATSVAWG LWAGDGMGRG
1310 1320 1330 1340 1350
ADDAYWQRRG IRPMSPDRAL DELAKALSHD ETFVAVADVD WERFAPAFTV
1360 1370 1380 1390 1400
SRPSLLLDGV PEARQALAAP VGAPAPGDAA VAPTGQSSAL AAITALPEPE
1410 1420 1430 1440 1450
RRPALLTLVR THAAAVLGHS SPDRVAPGRA FTELGFDSLT AVQLRNQLST
1460 1470 1480 1490 1500
VVGNRLPATT VFDHPTPAAL AAHLHEAYLA PAEPAPTDWE GRVRRALAEL
1510 1520 1530 1540 1550
PLDRLRDAGV LDTVLRLTGI EPEPGSGGSD GGAADPGAEP EASIDDLDAE
1560
ALIRMALGPR NT
Length:1,562
Mass (Da):163,594
Last modified:May 1, 1999 - v1
Checksum:iDB4BA0DAAA15B63F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF079138 Genomic DNA. Translation: AAC69331.1.
LN881739 Genomic DNA. Translation: CUM38836.1.
PIRiT17411.
RefSeqiWP_055641629.1. NZ_LN881739.1.

Genome annotation databases

KEGGiag:AAC69331.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF079138 Genomic DNA. Translation: AAC69331.1.
LN881739 Genomic DNA. Translation: CUM38836.1.
PIRiT17411.
RefSeqiWP_055641629.1. NZ_LN881739.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3F5HX-ray1.75A/B1534-1562[»]
ProteinModelPortaliQ9ZGI3.
SMRiQ9ZGI3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61040N.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

KEGGiag:AAC69331.

Phylogenomic databases

KOiK16002.

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-18413.

Miscellaneous databases

EvolutionaryTraceiQ9ZGI3.

Family and domain databases

Gene3Di1.10.1200.10. 1 hit.
3.40.366.10. 2 hits.
3.40.47.10. 2 hits.
3.40.50.720. 1 hit.
InterProiIPR001227. Ac_transferase_dom.
IPR014043. Acyl_transferase.
IPR016035. Acyl_Trfase/lysoPLipase.
IPR032821. KAsynt_C_assoc.
IPR018201. Ketoacyl_synth_AS.
IPR014031. Ketoacyl_synth_C.
IPR014030. Ketoacyl_synth_N.
IPR016036. Malonyl_transacylase_ACP-bd.
IPR016040. NAD(P)-bd_dom.
IPR020801. PKS_acyl_transferase.
IPR020841. PKS_Beta-ketoAc_synthase_dom.
IPR013968. PKS_KR.
IPR020806. PKS_PP-bd.
IPR015083. Polyketide_synth_docking.
IPR009081. PP-bd_ACP.
IPR006162. Ppantetheine_attach_site.
IPR016039. Thiolase-like.
[Graphical view]
PfamiPF00698. Acyl_transf_1. 1 hit.
PF08990. Docking. 1 hit.
PF16197. KAsynt_C_assoc. 1 hit.
PF00109. ketoacyl-synt. 1 hit.
PF02801. Ketoacyl-synt_C. 1 hit.
PF08659. KR. 1 hit.
PF00550. PP-binding. 1 hit.
[Graphical view]
SMARTiSM00827. PKS_AT. 1 hit.
SM00825. PKS_KS. 1 hit.
SM00823. PKS_PP. 1 hit.
[Graphical view]
SUPFAMiSSF101173. SSF101173. 1 hit.
SSF47336. SSF47336. 1 hit.
SSF51735. SSF51735. 2 hits.
SSF52151. SSF52151. 2 hits.
SSF53901. SSF53901. 3 hits.
SSF55048. SSF55048. 1 hit.
PROSITEiPS50075. ACP_DOMAIN. 1 hit.
PS00606. B_KETOACYL_SYNTHASE. 1 hit.
PS00012. PHOSPHOPANTETHEINE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPIKA3_STRVZ
AccessioniPrimary (citable) accession number: Q9ZGI3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 8, 2016
Last sequence update: May 1, 1999
Last modified: November 2, 2016
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Type I modular polyketide synthases (PKSs) catalyze the step-wise condensation of simple carboxylic acid derivatives. Organizationally, type I PKSs are arranged into modules, wherein each module is comprised of a set of catalytic activities that is responsible for a single elongation of the polyketide chain and the appropriate reductive processing of the beta-keto functionality. A minimal elongation module contains an acyl transferase (AT) domain, an acyl-carrier protein (ACP) domain, and a ketosynthase (KS) domain. The AT domain is responsible for loading the methylmalonyl-CoA extender unit onto the phosphopantetheinylated ACP domain. Subsequently, the KS domain decarboxylates and then condenses the ACP-bound extender unit with the growing polyketide chain obtained from the preceding module to yield an ACP-bound beta-ketoacyl intermediate. In addition to the three core domains, each elongation module may contain up to three additional domains: a ketoreductase (KR), dehydratase (DH), and an enoyl reductase (ER) that are responsible for the reductive processing of the beta-keto functionality prior to the next extension step. The presence of a KR domain alone gives rise to a beta-hydroxyl functionality, the presence of both a KR and a DH domain generates an alkene, while the combination of KR, DH, and ER results in complete reduction to the alkane. Finally, a thioesterase (TE) domain, typically found at the terminus of the last elongation module, catalyzes the termination of polyketide biosynthesis. The activity of this domain results in cleavage of the acyl chain from the adjacent ACP and formation of the macrocyclic ring.1 Publication

Keywords - Technical termi

3D-structure, Multifunctional enzyme

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.