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Protein

Narbonolide/10-deoxymethynolide synthase PikA4, module 6

Gene

pikAIV

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. The thioesterase can use a series of diketide-N-acetylcysteamine (SNAC) thioesters, but has a strong preference for the 2-methyl-3-ketopentanoyl-SNAC over the stereoisomers of 2-methyl-3-hydroxyacyl-SNAC (PubMed:12379101, PubMed:12733905).1 Publication6 Publications

Catalytic activityi

Malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH = 10-deoxymethynolide + 6 CoA + 6 CO2 + 5 NADP+ + 2 H2O.3 Publications1 Publication
Malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH = narbonolide + 7 CoA + 7 CO2 + 5 NADP+ + 2 H2O.3 Publications1 Publication

Cofactori

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

Enzyme regulationi

Irreversibly inhibited by (2S,3R,4S)-2,4-dihydroxy-3-methylhexyl-phosphonic acid and (3R,4S)-4-hydroxy-3-methyl-2-oxohexyl-phosphonic acid.1 Publication

Kineticsi

Kcat is 56 min(-1) for thioesterase activity with 2-methyl-3-ketopentanoyl-SNAC as substrate. Kcat is 7.9 min(-1) for thioesterase activity with (2S,3R)-2-methyl-3-hydroxyacyl-SNAC as substrate. Kcat is 4.3 min(-1) for thioesterase activity with (2R,3S)-2-methyl-3-hydroxyacyl-SNAC as substrate. Kcat is 2.6 min(-1) for thioesterase activity with (2S,3S)-2-methyl-3-hydroxyacyl-SNAC as substrate. Kcat is 1.8 min(-1) for thioesterase activity with (2R,3R)-2-methyl-3-hydroxyacyl-SNAC as substrate.1 Publication

  1. KM=7.3 mM for (2R,3S)-2-methyl-3-hydroxyacyl-SNAC (thioesterase activity)1 Publication
  2. KM=13 mM for (2S,3S)-2-methyl-3-hydroxyacyl-SNAC (thioesterase activity)1 Publication
  3. KM=15 mM for 2-methyl-3-ketopentanoyl-SNAC (thioesterase activity)1 Publication
  4. KM=16 mM for (2R,3R)-2-methyl-3-hydroxyacyl-SNAC (thioesterase activity)1 Publication
  5. KM=21 mM for (2S,3R)-2-methyl-3-hydroxyacyl-SNAC (thioesterase activity)1 Publication

    pH dependencei

    Optimum pH is between 8 and 8.4 (PubMed:12379101). In the thioesterase domain, the size of the substrate channel increases with increasing pH (PubMed:12379102).2 Publications

    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)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei207 – 2071For beta-ketoacyl synthase activityPROSITE-ProRule annotation
    Active sitei652 – 6521Acyl-ester intermediate; for acyltransferase activityBy similarity1 Publication
    Binding sitei1125 – 11251Substrate1 Publication
    Active sitei1196 – 11961Nucleophile; for thioesterase activityBy similarity1 Publication1 Publication
    Binding sitei1197 – 11971Substrate; via amide nitrogen2 Publications
    Binding sitei1224 – 12241SubstrateBy similarity
    Active sitei1316 – 13161Proton acceptor; for thioesterase activityBy similarity2 Publications

    GO - Molecular functioni

    • hydrolase activity, acting on ester bonds 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-18414.

    Protein family/group databases

    ESTHERistrve-PIKAIV. Thioesterase.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Narbonolide/10-deoxymethynolide synthase PikA4, module 6Curated (EC:2.3.1.2393 Publications1 Publication, EC:2.3.1.2403 Publications1 Publication)
    Alternative name(s):
    Narbonolide/10-deoxymethynolide synthase PikAIVCurated
    Pikromycin polyketide synthase component PikAIV1 Publication
    Short name:
    Pikromycin PKS component PikAIV1 Publication
    Type I modular polyketide synthase PikAIV1 Publication
    Short name:
    PKS1 Publication
    Gene namesi
    Name:pikAIV1 Publication
    OrganismiStreptomyces venezuelae
    Taxonomic identifieri54571 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaStreptomycetalesStreptomycetaceaeStreptomyces

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi207 – 2071C → A: Unable to catalyze the biosynthesis of the 14-membered ring macrolactone narbonolide, however it is able to produce the 12-membered ring macrolactone 10-deoxymethynolide. 1 Publication
    Mutagenesisi652 – 6521S → A: Unable to catalyze the biosynthesis of the 14-membered ring macrolactone narbonolide, however it is able to produce the 12-membered ring macrolactone 10-deoxymethynolide. 1 Publication
    Mutagenesisi980 – 9801S → A: Unable to catalyze the biosynthesis of the 14-membered ring macrolactone narbonolide, however it is able to produce the 12-membered ring macrolactone 10-deoxymethynolide. 1 Publication
    Mutagenesisi1196 – 11961S → A: Loss of thioesterase activity. Unable to catalyze the biosynthesis of the 14-membered ring macrolactone narbonolide and 12-membered ring macrolactone 10-deoxymethynolide. The 10-deoxymethynolide molecule is removed from the catalytic triad, does not reach the most hydrophobic region of the channel, disrupts the hydrophilic-barrier water network and is rotated with respect the phosphopentaketide. 3 Publications
    Mutagenesisi1224 – 12241D → A: Retains significant albeit reduced thioesterase activity. 1 Publication
    Mutagenesisi1235 – 12351E → N: Only relatively minor changes in the thioesterase activity. 10-fold reduction in the kcat/Km for ketoester; when associated with E-1239. 1 Publication
    Mutagenesisi1239 – 12391R → E: 10-fold reduction in the kcat/Km for ketoester; when associated with N-1235. 1 Publication
    Mutagenesisi1239 – 12391R → N: 3-fold decrease fo the catalytic efficiency and 3-fold increase of affinity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 13461346Narbonolide/10-deoxymethynolide synthase PikA4, module 6PRO_0000436360Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei980 – 9801O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation1 Publication

    Keywords - PTMi

    Phosphopantetheine, Phosphoprotein

    Interactioni

    Subunit structurei

    Homodimer (PubMed:12379102, PubMed:16969373, PubMed:16969372, 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 Publication4 Publications

    Structurei

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1MN6X-ray2.20A/B1049-1346[»]
    1MNAX-ray1.80A/B1049-1346[»]
    1MNQX-ray2.20A/B1049-1346[»]
    2H7XX-ray1.85A/B1049-1346[»]
    2H7YX-ray2.10A/B1049-1346[»]
    2HFJX-ray1.95A/B1049-1346[»]
    2HFKX-ray1.79A/B1049-1346[»]
    3F5HX-ray1.75A/B1-37[»]
    ProteinModelPortaliQ9ZGI2.
    SMRiQ9ZGI2. Positions 34-906, 1057-1339.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9ZGI2.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini943 – 101775Acyl carrierPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni37 – 13321296Module 6CuratedAdd
    BLAST
    Regioni37 – 464428Beta-ketoacyl synthaseCuratedAdd
    BLAST
    Regioni562 – 844283AcyltransferaseCuratedAdd
    BLAST
    Regioni1127 – 1332206ThioesteraseCuratedAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili3 – 3230Sequence analysisAdd
    BLAST

    Domaini

    Cells lacking the TE domain are unable to produce methymycin, neomethymycin, narbomycin and pikromycin.1 Publication

    Sequence similaritiesi

    Contains 1 acyl carrier domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    KOiK16003.

    Family and domain databases

    Gene3Di1.10.1200.10. 1 hit.
    3.40.366.10. 2 hits.
    3.40.47.10. 2 hits.
    3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    IPR001227. 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.
    IPR020801. PKS_acyl_transferase.
    IPR020841. PKS_Beta-ketoAc_synthase_dom.
    IPR020806. PKS_PP-bd.
    IPR020802. PKS_thioesterase.
    IPR009081. PP-bd_ACP.
    IPR001031. Thioesterase.
    IPR016039. Thiolase-like.
    [Graphical view]
    PfamiPF00698. Acyl_transf_1. 1 hit.
    PF16197. KAsynt_C_assoc. 1 hit.
    PF00109. ketoacyl-synt. 1 hit.
    PF02801. Ketoacyl-synt_C. 1 hit.
    PF00550. PP-binding. 1 hit.
    PF00975. Thioesterase. 1 hit.
    [Graphical view]
    SMARTiSM00827. PKS_AT. 1 hit.
    SM00825. PKS_KS. 1 hit.
    SM00823. PKS_PP. 1 hit.
    SM00824. PKS_TE. 1 hit.
    [Graphical view]
    SUPFAMiSSF47336. SSF47336. 1 hit.
    SSF52151. SSF52151. 2 hits.
    SSF53474. SSF53474. 2 hits.
    SSF53901. SSF53901. 2 hits.
    SSF55048. SSF55048. 1 hit.
    PROSITEiPS50075. ACP_DOMAIN. 1 hit.
    PS00606. B_KETOACYL_SYNTHASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9ZGI2-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTSSNEQLVD ALRASLKENE ELRKESRRRA DRRQEPMAIV GMSCRFAGGI
    60 70 80 90 100
    RSPEDLWDAV AAGKDLVSEV PEERGWDIDS LYDPVPGRKG TTYVRNAAFL
    110 120 130 140 150
    DDAAGFDAAF FGISPREALA MDPQQRQLLE ASWEVFERAG IDPASVRGTD
    160 170 180 190 200
    VGVYVGCGYQ DYAPDIRVAP EGTGGYVVTG NSSAVASGRI AYSLGLEGPA
    210 220 230 240 250
    VTVDTACSSS LVALHLALKG LRNGDCSTAL VGGVAVLATP GAFIEFSSQQ
    260 270 280 290 300
    AMAADGRTKG FASAADGLAW GEGVAVLLLE RLSDARRKGH RVLAVVRGSA
    310 320 330 340 350
    INQDGASNGL TAPHGPSQQH LIRQALADAR LTSSDVDVVE GHGTGTRLGD
    360 370 380 390 400
    PIEAQALLAT YGQGRAPGQP LRLGTLKSNI GHTQAASGVA GVIKMVQALR
    410 420 430 440 450
    HGVLPKTLHV DEPTDQVDWS AGSVELLTEA VDWPERPGRL RRAGVSAFGV
    460 470 480 490 500
    GGTNAHVVLE EAPAVEESPA VEPPAGGGVV PWPVSAKTSA ALDAQIGQLA
    510 520 530 540 550
    AYAEDRTDVD PAVAARALVD SRTAMEHRAV AVGDSREALR DALRMPEGLV
    560 570 580 590 600
    RGTVTDPGRV AFVFPGQGTQ WAGMGAELLD SSPEFAAAMA ECETALSPYV
    610 620 630 640 650
    DWSLEAVVRQ APSAPTLDRV DVVQPVTFAV MVSLAKVWQH HGITPEAVIG
    660 670 680 690 700
    HSQGEIAAAY VAGALTLDDA ARVVTLRSKS IAAHLAGKGG MISLALSEEA
    710 720 730 740 750
    TRQRIENLHG LSIAAVNGPT ATVVSGDPTQ IQELAQACEA DGIRARIIPV
    760 770 780 790 800
    DYASHSAHVE TIENELADVL AGLSPQTPQV PFFSTLEGTW ITEPALDGGY
    810 820 830 840 850
    WYRNLRHRVG FAPAVETLAT DEGFTHFIEV SAHPVLTMTL PDKVTGLATL
    860 870 880 890 900
    RREDGGQHRL TTSLAEAWAN GLALDWASLL PATGALSPAV PDLPTYAFQH
    910 920 930 940 950
    RSYWISPAGP GEAPAHTASG REAVAETGLA WGPGAEDLDE EGRRSAVLAM
    960 970 980 990 1000
    VMRQAASVLR CDSPEEVPVD RPLREIGFDS LTAVDFRNRV NRLTGLQLPP
    1010 1020 1030 1040 1050
    TVVFQHPTPV ALAERISDEL AERNWAVAEP SDHEQAEEEK AAAPAGARSG
    1060 1070 1080 1090 1100
    ADTGAGAGMF RALFRQAVED DRYGEFLDVL AEASAFRPQF ASPEACSERL
    1110 1120 1130 1140 1150
    DPVLLAGGPT DRAEGRAVLV GCTGTAANGG PHEFLRLSTS FQEERDFLAV
    1160 1170 1180 1190 1200
    PLPGYGTGTG TGTALLPADL DTALDAQARA ILRAAGDAPV VLLGHSGGAL
    1210 1220 1230 1240 1250
    LAHELAFRLE RAHGAPPAGI VLVDPYPPGH QEPIEVWSRQ LGEGLFAGEL
    1260 1270 1280 1290 1300
    EPMSDARLLA MGRYARFLAG PRPGRSSAPV LLVRASEPLG DWQEERGDWR
    1310 1320 1330 1340
    AHWDLPHTVA DVPGDHFTMM RDHAPAVAEA VLSWLDAIEG IEGAGK
    Length:1,346
    Mass (Da):141,914
    Last modified:May 1, 1999 - v1
    Checksum:i3E149C8044FBE5F2
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF079138 Genomic DNA. Translation: AAC69332.1.
    PIRiT17412.

    Genome annotation databases

    KEGGiag:AAC69332.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF079138 Genomic DNA. Translation: AAC69332.1.
    PIRiT17412.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1MN6X-ray2.20A/B1049-1346[»]
    1MNAX-ray1.80A/B1049-1346[»]
    1MNQX-ray2.20A/B1049-1346[»]
    2H7XX-ray1.85A/B1049-1346[»]
    2H7YX-ray2.10A/B1049-1346[»]
    2HFJX-ray1.95A/B1049-1346[»]
    2HFKX-ray1.79A/B1049-1346[»]
    3F5HX-ray1.75A/B1-37[»]
    ProteinModelPortaliQ9ZGI2.
    SMRiQ9ZGI2. Positions 34-906, 1057-1339.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein family/group databases

    ESTHERistrve-PIKAIV. Thioesterase.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    KEGGiag:AAC69332.

    Phylogenomic databases

    KOiK16003.

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-18414.

    Miscellaneous databases

    EvolutionaryTraceiQ9ZGI2.

    Family and domain databases

    Gene3Di1.10.1200.10. 1 hit.
    3.40.366.10. 2 hits.
    3.40.47.10. 2 hits.
    3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    IPR001227. 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.
    IPR020801. PKS_acyl_transferase.
    IPR020841. PKS_Beta-ketoAc_synthase_dom.
    IPR020806. PKS_PP-bd.
    IPR020802. PKS_thioesterase.
    IPR009081. PP-bd_ACP.
    IPR001031. Thioesterase.
    IPR016039. Thiolase-like.
    [Graphical view]
    PfamiPF00698. Acyl_transf_1. 1 hit.
    PF16197. KAsynt_C_assoc. 1 hit.
    PF00109. ketoacyl-synt. 1 hit.
    PF02801. Ketoacyl-synt_C. 1 hit.
    PF00550. PP-binding. 1 hit.
    PF00975. Thioesterase. 1 hit.
    [Graphical view]
    SMARTiSM00827. PKS_AT. 1 hit.
    SM00825. PKS_KS. 1 hit.
    SM00823. PKS_PP. 1 hit.
    SM00824. PKS_TE. 1 hit.
    [Graphical view]
    SUPFAMiSSF47336. SSF47336. 1 hit.
    SSF52151. SSF52151. 2 hits.
    SSF53474. SSF53474. 2 hits.
    SSF53901. SSF53901. 2 hits.
    SSF55048. SSF55048. 1 hit.
    PROSITEiPS50075. ACP_DOMAIN. 1 hit.
    PS00606. B_KETOACYL_SYNTHASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    1. "A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: architecture of metabolic diversity."
      Xue Y., Zhao L., Liu H.W., Sherman D.H.
      Proc. Natl. Acad. Sci. U.S.A. 95:12111-12116(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PATHWAY.
      Strain: ATCC 15439 / DSM 41110 / IMRU3627 / M-2140.
    2. "Elucidating the mechanism of chain termination switching in the picromycin/methymycin polyketide synthase."
      Tang L., Fu H., Betlach M.C., McDaniel R.
      Chem. Biol. 6:553-558(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY.
    3. "Alternative modular polyketide synthase expression controls macrolactone structure."
      Xue Y., Sherman D.H.
      Nature 403:571-575(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DOMAIN.
      Strain: ATCC 15439 / DSM 41110 / IMRU3627 / M-2140.
    4. "Expression, site-directed mutagenesis, and steady state kinetic analysis of the terminal thioesterase domain of the methymycin/picromycin polyketide synthase."
      Lu H., Tsai S.C., Khosla C., Cane D.E.
      Biochemistry 41:12590-12597(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF SER-1196; ASP-1224; GLU-1235 AND ARG-1239, SUBSTRATE SPECIFICITY.
    5. "Expression and kinetic analysis of the substrate specificity of modules 5 and 6 of the picromycin/methymycin polyketide synthase."
      Yin Y., Lu H., Khosla C., Cane D.E.
      J. Am. Chem. Soc. 125:5671-5676(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY.
    6. "Interrogating the molecular basis for multiple macrolactone ring formation by the pikromycin polyketide synthase."
      Kittendorf J.D., Beck B.J., Buchholz T.J., Seufert W., Sherman D.H.
      Chem. Biol. 14:944-954(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-207; SER-652; SER-980 AND SER-1196, COFACTOR, ACTIVE SITE.
    7. "The methymycin/pikromycin pathway: a model for metabolic diversity in natural product biosynthesis."
      Kittendorf J.D., Sherman D.H.
      Bioorg. Med. Chem. 17:2137-2146(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PATHWAY, SUBUNIT.
    8. "Insights into channel architecture and substrate specificity from crystal structures of two macrocycle-forming thioesterases of modular polyketide synthases."
      Tsai S.-C., Lu H., Cane D.E., Khosla C., Stroud R.M.
      Biochemistry 41:12598-12606(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1049-1346, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
    9. "Structural and mechanistic insights into polyketide macrolactonization from polyketide-based affinity labels."
      Giraldes J.W., Akey D.L., Kittendorf J.D., Sherman D.H., Smith J.L., Fecik R.A.
      Nat. Chem. Biol. 2:531-536(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1049-1346 IN COMPLEX WITH SUBSTRATE ANALOGS, ENZYME REGULATION, ACTIVE SITE, SUBUNIT.
    10. "Structural basis for macrolactonization by the pikromycin thioesterase."
      Akey D.L., Kittendorf J.D., Giraldes J.W., Fecik R.A., Sherman D.H., Smith J.L.
      Nat. Chem. Biol. 2:537-542(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 1049-1346 OF WILD-TYPE AND MUTANT ALA-1196 IN COMPLEX WITH SUBSTRATE ANALOGS, FUNCTION, MUTAGENESIS OF SER-1196, REACTION MECHANISM, ACTIVE SITE, SUBUNIT.
    11. "Structural basis for binding specificity between subclasses of modular polyketide synthase docking domains."
      Buchholz T.J., Geders T.W., Bartley F.E., Reynolds K.A., Smith J.L., Sherman D.H.
      ACS Chem. Biol. 4:41-52(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-37, SUBUNIT.

    Entry informationi

    Entry nameiPIKA4_STRVZ
    AccessioniPrimary (citable) accession number: Q9ZGI2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 8, 2016
    Last sequence update: May 1, 1999
    Last modified: June 8, 2016
    This is version 101 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.