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Protein

Narbonolide/10-deoxymethynolide synthase PikA2, modules 3 and 4

Gene

pikAII

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

Functioni

Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin/neomethymycin and pikromycin/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

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.2 Publications
C2-type beta-ketoacyl reductase 1 is unable to bind NADP and seems to act as a racemase.1 Publication

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 2 phosphopantetheines 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 sitei208Acyl-thioester intermediate; for beta-ketoacyl synthase 1 activityPROSITE-ProRule annotation1
Active sitei662Acyl-ester intermediate; for acyltransferase 1 activityPROSITE-ProRule annotation1
Active sitei1313For C2-type beta-ketoacyl reductase 1 and probable racemase activitiesBy similarity1 Publication1
Active sitei1712Acyl-thioester intermediate; for beta-ketoacyl synthase 2 activityPROSITE-ProRule annotation1
Active sitei2159Acyl-ester intermediate; for acyltransferase 2 activityPROSITE-ProRule annotation1
Active sitei2460Proton acceptor; for dehydratase activityBy similarity1
Active sitei2629Proton donor; for dehydratase activityBy similarity1
Active sitei3005For enoyl reductase activityBy similarity1
Binding sitei3388NADP (Beta-ketoacyl reductase 2)By similarity1
Active sitei3427For beta-ketoacyl reductase 2 activityCurated1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi3092 – 3109NADP (Enoyl reductase)By similarityAdd BLAST18
Nucleotide bindingi3285 – 3288NADP (Beta-ketoacyl reductase 2)Curated4
Nucleotide bindingi3309 – 3312NADP (Beta-ketoacyl reductase 2)Curated4
Nucleotide bindingi3338 – 3339NADP (Beta-ketoacyl reductase 2)Curated2
Nucleotide bindingi3412 – 3413NADP (Beta-ketoacyl reductase 2)Curated2

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionAcyltransferase, Multifunctional enzyme, Transferase
Biological processAntibiotic biosynthesis
LigandNADP

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-18412

Names & Taxonomyi

Protein namesi
Recommended name:
Narbonolide/10-deoxymethynolide synthase PikA2, modules 3 and 4Curated (EC:2.3.1.2391 Publication1 Publication, EC:2.3.1.2401 Publication1 Publication)
Alternative name(s):
Narbonolide/10-deoxymethynolide synthase PikAIICurated
Pikromycin polyketide synthase component PikAII1 Publication
Short name:
Pikromycin PKS component PikAII1 Publication
Type I modular polyketide synthase PikAII1 Publication
Short name:
PKS1 Publication
Gene namesi
Name:pikAII1 Publication
OrganismiStreptomyces venezuelae
Taxonomic identifieri54571 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaStreptomycetalesStreptomycetaceaeStreptomyces

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004363581 – 3739Narbonolide/10-deoxymethynolide synthase PikA2, modules 3 and 4Add BLAST3739

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1480O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation1
Modified residuei3605O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation1

Keywords - PTMi

Phosphopantetheine, Phosphoprotein

Interactioni

Subunit structurei

Homodimer (PubMed:21570406). 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

Structurei

Secondary structure

13739
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9ZGI4
SMRiQ9ZGI4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1445 – 1520Carrier 1PROSITE-ProRule annotationAdd BLAST76
Domaini3570 – 3645Carrier 2PROSITE-ProRule annotationAdd BLAST76

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni38 – 1517Module 3CuratedAdd BLAST1480
Regioni38 – 466Beta-ketoacyl synthase 1CuratedAdd BLAST429
Regioni572 – 877Acyltransferase 1CuratedAdd BLAST306
Regioni1150 – 1343C2-type beta-ketoacyl reductase 11 PublicationAdd BLAST194
Regioni1542 – 3642Module 4CuratedAdd BLAST2101
Regioni1542 – 1970Beta-ketoacyl synthase 2CuratedAdd BLAST429
Regioni2069 – 2374Acyltransferase 2CuratedAdd BLAST306
Regioni2428 – 2703DehydrataseCuratedAdd BLAST276
Regioni2959 – 3267Enoyl reductaseCuratedAdd BLAST309
Regioni3277 – 3458Beta-ketoacyl reductase 2CuratedAdd BLAST182

Keywords - Domaini

Repeat

Phylogenomic databases

KOiK16001

Family and domain databases

Gene3Di1.10.1200.10, 2 hits
3.40.366.10, 2 hits
3.40.47.10, 2 hits
InterProiView protein in InterPro
IPR001227 Ac_transferase_dom_sf
IPR036736 ACP-like_sf
IPR014043 Acyl_transferase
IPR016035 Acyl_Trfase/lysoPLipase
IPR013154 ADH_N
IPR011032 GroES-like_sf
IPR032821 KAsynt_C_assoc
IPR018201 Ketoacyl_synth_AS
IPR014031 Ketoacyl_synth_C
IPR014030 Ketoacyl_synth_N
IPR016036 Malonyl_transacylase_ACP-bd
IPR036291 NAD(P)-bd_dom_sf
IPR020801 PKS_acyl_transferase
IPR020841 PKS_Beta-ketoAc_synthase_dom
IPR020807 PKS_dehydratase
IPR020843 PKS_ER
IPR013968 PKS_KR
IPR020806 PKS_PP-bd
IPR015083 Polyketide_synth_docking
IPR009081 PP-bd_ACP
IPR006162 Ppantetheine_attach_site
IPR002364 Quin_OxRdtase/zeta-crystal_CS
IPR016039 Thiolase-like
PfamiView protein in Pfam
PF00698 Acyl_transf_1, 2 hits
PF08240 ADH_N, 1 hit
PF08990 Docking, 1 hit
PF16197 KAsynt_C_assoc, 2 hits
PF00109 ketoacyl-synt, 2 hits
PF02801 Ketoacyl-synt_C, 2 hits
PF08659 KR, 2 hits
PF00550 PP-binding, 2 hits
PF14765 PS-DH, 1 hit
SMARTiView protein in SMART
SM00827 PKS_AT, 2 hits
SM00826 PKS_DH, 1 hit
SM00829 PKS_ER, 1 hit
SM00825 PKS_KS, 2 hits
SM00823 PKS_PP, 2 hits
SUPFAMiSSF47336 SSF47336, 2 hits
SSF50129 SSF50129, 1 hit
SSF51735 SSF51735, 5 hits
SSF52151 SSF52151, 4 hits
SSF53901 SSF53901, 4 hits
SSF55048 SSF55048, 2 hits
PROSITEiView protein in PROSITE
PS00606 B_KETOACYL_SYNTHASE, 2 hits
PS50075 CARRIER, 2 hits
PS00012 PHOSPHOPANTETHEINE, 2 hits
PS01162 QOR_ZETA_CRYSTAL, 1 hit

Sequencei

Sequence statusi: Complete.

Q9ZGI4-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSTVNEEKYL DYLRRATADL HEARGRLREL EAKAGEPVAI VGMACRLPGG
60 70 80 90 100
VASPEDLWRL VAGGEDAISE FPQDRGWDVE GLYDPNPEAT GKSYAREAGF
110 120 130 140 150
LYEAGEFDAD FFGISPREAL AMDPQQRLLL EASWEAFEHA GIPAATARGT
160 170 180 190 200
SVGVFTGVMY HDYATRLTDV PEGIEGYLGT GNSGSVASGR VAYTLGLEGP
210 220 230 240 250
AVTVDTACSS SLVALHLAVQ ALRKGEVDMA LAGGVTVMST PSTFVEFSRQ
260 270 280 290 300
RGLAPDGRSK SFSSTADGTS WSEGVGVLLV ERLSDARRKG HRILAVVRGT
310 320 330 340 350
AVNQDGASSG LTAPNGPSQQ RVIRRALADA RLTTSDVDVV EAHGTGTRLG
360 370 380 390 400
DPIEAQAVIA TYGQGRDGEQ PLRLGSLKSN IGHTQAAAGV SGVIKMVQAM
410 420 430 440 450
RHGVLPKTLH VEKPTDQVDW SAGAVELLTE AMDWPDKGDG GLRRAAVSSF
460 470 480 490 500
GVSGTNAHVV LEEAPAAEET PASEATPAVE PSVGAGLVPW LVSAKTPAAL
510 520 530 540 550
DAQIGRLAAF ASQGRTDAAD PGAVARVLAG GRAEFEHRAV VLGTGQDDFA
560 570 580 590 600
QALTAPEGLI RGTPSDVGRV AFVFPGQGTQ WAGMGAELLD VSKEFAAAMA
610 620 630 640 650
ECESALSRYV DWSLEAVVRQ APGAPTLERV DVVQPVTFAV MVSLAKVWQH
660 670 680 690 700
HGVTPQAVVG HSQGEIAAAY VAGALTLDDA ARVVTLRSKS IAAHLAGKGG
710 720 730 740 750
MISLALSEEA TRQRIENLHG LSIAAVNGPT ATVVSGDPTQ IQELAQACEA
760 770 780 790 800
DGVRARIIPV DYASHSAHVE TIESELAEVL AGLSPRTPEV PFFSTLEGAW
810 820 830 840 850
ITEPVLDGTY WYRNLRHRVG FAPAVETLAT DEGFTHFIEV SAHPVLTMTL
860 870 880 890 900
PETVTGLGTL RREQGGQERL VTSLAEAWTN GLTIDWAPVL PTATGHHPEL
910 920 930 940 950
PTYAFQRRHY WLHDSPAVQG SVQDSWRYRI DWKRLAVADA SERAGLSGRW
960 970 980 990 1000
LVVVPEDRSA EAAPVLAALS GAGADPVQLD VSPLGDRQRL AATLGEALAA
1010 1020 1030 1040 1050
AGGAVDGVLS LLAWDESAHP GHPAPFTRGT GATLTLVQAL EDAGVAAPLW
1060 1070 1080 1090 1100
CVTHGAVSVG RADHVTSPAQ AMVWGMGRVA ALEHPERWGG LIDLPSDADR
1110 1120 1130 1140 1150
AALDRMTTVL AGGTGEDQVA VRASGLLARR LVRASLPAHG TASPWWQADG
1160 1170 1180 1190 1200
TVLVTGAEEP AAAEAARRLA RDGAGHLLLH TTPSGSEGAE GTSGAAEDSG
1210 1220 1230 1240 1250
LAGLVAELAD LGATATVVTC DLTDAEAAAR LLAGVSDAHP LSAVLHLPPT
1260 1270 1280 1290 1300
VDSEPLAATD ADALARVVTA KATAALHLDR LLREAAAAGG RPPVLVLFSS
1310 1320 1330 1340 1350
VAAIWGGAGQ GAYAAGTAFL DALAGQHRAD GPTVTSVAWS PWEGSRVTEG
1360 1370 1380 1390 1400
ATGERLRRLG LRPLAPATAL TALDTALGHG DTAVTIADVD WSSFAPGFTT
1410 1420 1430 1440 1450
ARPGTLLADL PEARRALDEQ QSTTAADDTV LSRELGALTG AEQQRRMQEL
1460 1470 1480 1490 1500
VREHLAVVLN HPSPEAVDTG RAFRDLGFDS LTAVELRNRL KNATGLALPA
1510 1520 1530 1540 1550
TLVFDYPTPR TLAEFLLAEI LGEQAGAGEQ LPVDGGVDDE PVAIVGMACR
1560 1570 1580 1590 1600
LPGGVASPED LWRLVAGGED AISGFPQDRG WDVEGLYDPD PDASGRTYCR
1610 1620 1630 1640 1650
AGGFLDEAGE FDADFFGISP REALAMDPQQ RLLLETSWEA VEDAGIDPTS
1660 1670 1680 1690 1700
LQGQQVGVFA GTNGPHYEPL LRNTAEDLEG YVGTGNAASI MSGRVSYTLG
1710 1720 1730 1740 1750
LEGPAVTVDT ACSSSLVALH LAVQALRKGE CGLALAGGVT VMSTPTTFVE
1760 1770 1780 1790 1800
FSRQRGLAED GRSKAFAASA DGFGPAEGVG MLLVERLSDA RRNGHRVLAV
1810 1820 1830 1840 1850
VRGSAVNQDG ASNGLTAPNG PSQQRVIRRA LADARLTTAD VDVVEAHGTG
1860 1870 1880 1890 1900
TRLGDPIEAQ ALIATYGQGR DTEQPLRLGS LKSNIGHTQA AAGVSGIIKM
1910 1920 1930 1940 1950
VQAMRHGVLP KTLHVDRPSD QIDWSAGTVE LLTEAMDWPR KQEGGLRRAA
1960 1970 1980 1990 2000
VSSFGISGTN AHIVLEEAPV DEDAPADEPS VGGVVPWLVS AKTPAALDAQ
2010 2020 2030 2040 2050
IGRLAAFASQ GRTDAADPGA VARVLAGGRA QFEHRAVALG TGQDDLAAAL
2060 2070 2080 2090 2100
AAPEGLVRGV ASGVGRVAFV FPGQGTQWAG MGAELLDVSK EFAAAMAECE
2110 2120 2130 2140 2150
AALAPYVDWS LEAVVRQAPG APTLERVDVV QPVTFAVMVS LAKVWQHHGV
2160 2170 2180 2190 2200
TPQAVVGHSQ GEIAAAYVAG ALSLDDAARV VTLRSKSIGA HLAGQGGMLS
2210 2220 2230 2240 2250
LALSEAAVVE RLAGFDGLSV AAVNGPTATV VSGDPTQIQE LAQACEADGV
2260 2270 2280 2290 2300
RARIIPVDYA SHSAHVETIE SELADVLAGL SPQTPQVPFF STLEGAWITE
2310 2320 2330 2340 2350
PALDGGYWYR NLRHRVGFAP AVETLATDEG FTHFVEVSAH PVLTMALPET
2360 2370 2380 2390 2400
VTGLGTLRRD NGGQHRLTTS LAEAWANGLT VDWASLLPTT TTHPDLPTYA
2410 2420 2430 2440 2450
FQTERYWPQP DLSAAGDITS AGLGAAEHPL LGAAVALADS DGCLLTGSLS
2460 2470 2480 2490 2500
LRTHPWLADH AVAGTVLLPG TAFVELAFRA GDQVGCDLVE ELTLDAPLVL
2510 2520 2530 2540 2550
PRRGAVRVQL SVGASDESGR RTFGLYAHPE DAPGEAEWTR HATGVLAARA
2560 2570 2580 2590 2600
DRTAPVADPE AWPPPGAEPV DVDGLYERFA ANGYGYGPLF QGVRGVWRRG
2610 2620 2630 2640 2650
DEVFADVALP AEVAGAEGAR FGLHPALLDA AVQAAGAGRG VRRGHAAAVR
2660 2670 2680 2690 2700
LERDLLYAVG ATALRVRLAP AGPDTVSVSA ADSSGQPVFA ADSLTVLPVD
2710 2720 2730 2740 2750
PAQLAAFSDP TLDALHLLEW TAWDGAAQAL PGAVVLGGDA DGLAAALRAG
2760 2770 2780 2790 2800
GTEVLSFPDL TDLVEAVDRG ETPAPATVLV ACPAAGPDGP EHVREALHGS
2810 2820 2830 2840 2850
LALMQAWLAD ERFTDGRLVL VTRDAVAARS GDGLRSTGQA AVWGLGRSAQ
2860 2870 2880 2890 2900
TESPGRFVLL DLAGEARTAG DATAGDGLTT GDATVGGTSG DAALGSALAT
2910 2920 2930 2940 2950
ALGSGEPQLA LRDGALLVPR LARAAAPAAA DGLAAADGLA ALPLPAAPAL
2960 2970 2980 2990 3000
WRLEPGTDGS LESLTAAPGD AETLAPEPLG PGQVRIAIRA TGLNFRDVLI
3010 3020 3030 3040 3050
ALGMYPDPAL MGTEGAGVVT ATGPGVTHLA PGDRVMGLLS GAYAPVVVAD
3060 3070 3080 3090 3100
ARTVARMPEG WTFAQGASVP VVFLTAVYAL RDLADVKPGE RLLVHSAAGG
3110 3120 3130 3140 3150
VGMAAVQLAR HWGVEVHGTA SHGKWDALRA LGLDDAHIAS SRTLDFESAF
3160 3170 3180 3190 3200
RAASGGAGMD VVLNSLAREF VDASLRLLGP GGRFVEMGKT DVRDAERVAA
3210 3220 3230 3240 3250
DHPGVGYRAF DLGEAGPERI GEMLAEVIAL FEDGVLRHLP VTTWDVRRAR
3260 3270 3280 3290 3300
DAFRHVSQAR HTGKVVLTMP SGLDPEGTVL LTGGTGALGG IVARHVVGEW
3310 3320 3330 3340 3350
GVRRLLLVSR RGTDAPGAGE LVHELEALGA DVSVAACDVA DREALTAVLD
3360 3370 3380 3390 3400
SIPAEHPLTA VVHTAGVLSD GTLPSMTAED VEHVLRPKVD AAFLLDELTS
3410 3420 3430 3440 3450
TPGYDLAAFV MFSSAAAVFG GAGQGAYAAA NATLDALAWR RRTAGLPALS
3460 3470 3480 3490 3500
LGWGLWAETS GMTGGLSDTD RSRLARSGAT PMDSELTLSL LDAAMRRDDP
3510 3520 3530 3540 3550
ALVPIALDVA ALRAQQRDGM LAPLLSGLTR GSRVGGAPVN QRRAAAGGAG
3560 3570 3580 3590 3600
EADTDLGGRL AAMTPDDRVA HLRDLVRTHV ATVLGHGTPS RVDLERAFRD
3610 3620 3630 3640 3650
TGFDSLTAVE LRNRLNAATG LRLPATLVFD HPTPGELAGH LLDELATAAG
3660 3670 3680 3690 3700
GSWAEGTGSG DTASATDRQT TAALAELDRL EGVLASLAPA AGGRPELAAR
3710 3720 3730
LRALAAALGD DGDDATDLDE ASDDDLFSFI DKELGDSDF
Length:3,739
Mass (Da):387,178
Last modified:May 1, 1999 - v1
Checksum:i3D3910824DA5B080
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF079138 Genomic DNA Translation: AAC69330.1
PIRiT17410

Genome annotation databases

KEGGiag:AAC69330

Similar proteinsi

Entry informationi

Entry nameiPIKA2_STRVZ
AccessioniPrimary (citable) accession number: Q9ZGI4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 8, 2016
Last sequence update: May 1, 1999
Last modified: February 28, 2018
This is version 110 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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