PPSE_MYCTU
ID PPSE_MYCTU Reviewed; 1488 AA.
AC P9WQE1; L0TDU0; P96204; Q7D6E9;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Phenolphthiocerol/phthiocerol polyketide synthase subunit E {ECO:0000305};
DE EC=2.3.1.292 {ECO:0000269|PubMed:15749014, ECO:0000305|PubMed:20553505};
DE AltName: Full=(Phenol)carboxyphthiodiolenone synthase subunit E;
DE AltName: Full=Beta-ketoacyl-acyl-carrier-protein synthase I;
DE AltName: Full=Phthiocerol synthesis polyketide synthase type I PpsE;
GN Name=ppsE; OrderedLocusNames=Rv2935;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP INTERACTION WITH TESA.
RC STRAIN=H37Rv;
RX PubMed=15668773; DOI=10.1007/s00438-004-1088-3;
RA Rao A., Ranganathan A.;
RT "Interaction studies on proteins encoded by the phthiocerol dimycocerosate
RT locus of Mycobacterium tuberculosis.";
RL Mol. Genet. Genomics 272:571-579(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND PATHWAY.
RX PubMed=15749014; DOI=10.1016/j.molcel.2005.02.009;
RA Trivedi O.A., Arora P., Vats A., Ansari M.Z., Tickoo R., Sridharan V.,
RA Mohanty D., Gokhale R.S.;
RT "Dissecting the mechanism and assembly of a complex virulence mycobacterial
RT lipid.";
RL Mol. Cell 17:631-643(2005).
RN [5]
RP INTERACTION WITH MMPL7.
RX PubMed=16201014; DOI=10.1371/journal.ppat.0010002;
RA Jain M., Cox J.S.;
RT "Interaction between polyketide synthase and transporter suggests coupled
RT synthesis and export of virulence lipid in M. tuberculosis.";
RL PLoS Pathog. 1:e2-e2(2005).
RN [6]
RP PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19197369; DOI=10.1371/journal.ppat.1000289;
RA Astarie-Dequeker C., Le Guyader L., Malaga W., Seaphanh F.K., Chalut C.,
RA Lopez A., Guilhot C.;
RT "Phthiocerol dimycocerosates of M. tuberculosis participate in macrophage
RT invasion by inducing changes in the organization of plasma membrane
RT lipids.";
RL PLoS Pathog. 5:E1000289-E1000289(2009).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20553505; DOI=10.1111/j.1742-4658.2010.07688.x;
RA Simeone R., Leger M., Constant P., Malaga W., Marrakchi H., Daffe M.,
RA Guilhot C., Chalut C.;
RT "Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis
RT of phthiocerol dimycocerosates and related compounds in Mycobacterium
RT tuberculosis.";
RL FEBS J. 277:2715-2725(2010).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Part of the PpsABCDE complex involved in the biosynthesis of
CC the lipid core common to phthiocerols and phenolphthiocerols by
CC successive additions of malonyl-CoA or methylmalonyl-CoA extender units
CC (PubMed:15749014, PubMed:20553505). PpsA can accept as substrate the
CC activated forms of either icosanoyl (C20), docosanoyl (C22) or
CC lignoceroyl (C24) groups from FadD26, or a (4-hydroxyphenyl)-C17 or (4-
CC hydroxyphenyl)-C19 fatty acyl from FadD29 (PubMed:15749014,
CC PubMed:20553505). PpsA initiates the biosynthesis and extends its
CC substrate using a malonyl-CoA extender unit. The PpsB and PpsC proteins
CC add the second and third malonyl-CoA extender units. PpsD adds an (R)-
CC methylmalonyl unit and PpsE adds a second (R)-methylmalonyl unit. The
CC incorporation of the methylmalonyl units results in formation of two
CC branched methyl groups in the elongated product (PubMed:15749014).
CC {ECO:0000269|PubMed:15749014, ECO:0000269|PubMed:20553505}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (S)-methylmalonyl-CoA + 10 H(+) + icosanoyl-
CC [(phenol)carboxyphthiodiolenone synthase] + 3 malonyl-CoA + 5 NADPH =
CC C32-carboxyphthiodiolenone-[(phenol)carboxyphthiodiolenone synthase]
CC + 5 CO2 + 5 CoA + 2 H2O + 5 NADP(+); Xref=Rhea:RHEA:57748, Rhea:RHEA-
CC COMP:14985, Rhea:RHEA-COMP:14986, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57327, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:87848, ChEBI:CHEBI:142236;
CC EC=2.3.1.292; Evidence={ECO:0000269|PubMed:15749014,
CC ECO:0000305|PubMed:20553505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (S)-methylmalonyl-CoA + docosanoyl-
CC [(phenol)carboxyphthiodiolenone synthase] + 10 H(+) + 3 malonyl-CoA +
CC 5 NADPH = C34-carboxyphthiodiolenone-[(phenol)carboxyphthiodiolenone
CC synthase] + 5 CO2 + 5 CoA + 2 H2O + 5 NADP(+); Xref=Rhea:RHEA:57752,
CC Rhea:RHEA-COMP:14987, Rhea:RHEA-COMP:14988, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57327, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142237, ChEBI:CHEBI:142238;
CC EC=2.3.1.292; Evidence={ECO:0000269|PubMed:15749014,
CC ECO:0000305|PubMed:20553505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (S)-methylmalonyl-CoA + 17-(4-hydroxyphenyl)heptadecanoyl-
CC [(phenol)carboxyphthiodiolenone synthase] + 10 H(+) + 3 malonyl-CoA +
CC 5 NADPH = C35-(phenol)carboxyphthiodiolenone-
CC [(phenol)carboxyphthiodiolenone synthase] + 5 CO2 + 5 CoA + 2 H2O + 5
CC NADP(+); Xref=Rhea:RHEA:57756, Rhea:RHEA-COMP:14272, Rhea:RHEA-
CC COMP:14989, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57327, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133300,
CC ChEBI:CHEBI:142259; EC=2.3.1.292;
CC Evidence={ECO:0000269|PubMed:15749014, ECO:0000305|PubMed:20553505};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 (S)-methylmalonyl-CoA + 19-(4-hydroxyphenyl)nonadecanoyl-
CC [(phenol)carboxyphthiodiolenone synthase] + 10 H(+) + 3 malonyl-CoA +
CC 5 NADPH = C37-(phenol)carboxyphthiodiolenone-
CC [(phenol)carboxyphthiodiolenone synthase] + 5 CO2 + 5 CoA + 2 H2O + 5
CC NADP(+); Xref=Rhea:RHEA:57760, Rhea:RHEA-COMP:14273, Rhea:RHEA-
CC COMP:14990, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57327, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133301,
CC ChEBI:CHEBI:142260; EC=2.3.1.292;
CC Evidence={ECO:0000269|PubMed:15749014, ECO:0000305|PubMed:20553505};
CC -!- COFACTOR:
CC Name=NADP(+); Xref=ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:15749014};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:15749014, ECO:0000269|PubMed:19197369}.
CC -!- SUBUNIT: The C-terminal region interacts with TesA (PubMed:15668773).
CC Interacts with MmpL7 (PubMed:16201014). {ECO:0000269|PubMed:15668773,
CC ECO:0000269|PubMed:16201014}.
CC -!- DISRUPTION PHENOTYPE: Deletion of this gene results in phthiocerol
CC dimycocerosates (DIM) deficiency and decreases the ability of the
CC bacteria to infect macrophages. {ECO:0000269|PubMed:19197369}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
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DR EMBL; AL123456; CCP45738.1; -; Genomic_DNA.
DR PIR; C70984; C70984.
DR RefSeq; NP_217451.1; NC_000962.3.
DR RefSeq; WP_003900602.1; NZ_NVQJ01000015.1.
DR AlphaFoldDB; P9WQE1; -.
DR SMR; P9WQE1; -.
DR STRING; 83332.Rv2935; -.
DR iPTMnet; P9WQE1; -.
DR PaxDb; P9WQE1; -.
DR GeneID; 888210; -.
DR KEGG; mtu:Rv2935; -.
DR TubercuList; Rv2935; -.
DR eggNOG; COG1020; Bacteria.
DR eggNOG; COG3321; Bacteria.
DR OMA; WSQRCAG; -.
DR PhylomeDB; P9WQE1; -.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0034081; C:polyketide synthase complex; IMP:UniProtKB.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IDA:MTBBASE.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0071766; P:Actinobacterium-type cell wall biogenesis; IMP:UniProtKB.
DR GO; GO:0071770; P:DIM/DIP cell wall layer assembly; IDA:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:UniProtKB.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Fatty acid metabolism; Lipid metabolism;
KW Multifunctional enzyme; NADP; Oxidoreductase; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..1488
FT /note="Phenolphthiocerol/phthiocerol polyketide synthase
FT subunit E"
FT /id="PRO_0000406952"
FT DOMAIN 930..1004
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 6..389
FT /note="Beta-ketoacyl synthase"
FT /evidence="ECO:0000250"
FT REGION 551..868
FT /note="Acyltransferase"
FT /evidence="ECO:0000250"
FT ACT_SITE 184
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 641
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT BINDING 1286..1331
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 965
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1488 AA; 158745 MW; C6418D88A27BB701 CRC64;
MSIPENAIAV VGMAGRFPGA KDVSAFWSNL RRGKESIVTL SEQELRDAGV SDKTLADPAY
VRRAPLLDGI DEFDAGFFGF PPLAAQVLDP QHRLFLQCAW HALEDAGADP ARFDGSIGVY
GTSSPSGYLL HNLLSHRDPN AVLAEGLNFD QFSLFLQNDK DFLATRISHA FNLRGPSIAV
QTACSSSLVA VHLACLSLLS GECDMALAGG SSLCIPHRVG YFTSPGSMVS AVGHCRPFDV
RADGTVFGSG VGLVVLKPLA AAIDAGDRIH AVIRGSAINN DGSAKMGYAA PNPAAQADVI
AEAHAVSGID SSTVSYVECH GTGTPLGDPI EIQGLRAAFE VSQTSRSAPC VLGSVKSNIG
HLEVAAGIAG LIKTILCLKN KALPATLHYT SPNPELRLDQ SPFVVQSKYG PWECDGVRRA
GVSSFGVGGT NAHVVLEEAP AEASEVSAHA EPAGPQVILL SAQTAAALGE SRTALAAALE
TQDGPRLSDV AYTLARRRKH NVTMAAVVHD REHAATVLRA AEHDNVFVGE AAHDGEHGDR
ADAAPTSDRV VFLFPGQGAQ HVGMAKGLYD TEPVFAQHFD TCAAGFRDET GIDLHAEVFD
GTATDLERID RSQPALFTVE YALAKLVDTF GVRAGAYIGY STGEYIAATL AGVFDLQTAI
KTVSLRARLM HESPPGAMVA VALGPDDVTQ YLPPEVELSA VNDPGNCVVA GPKDQIRALR
QRLTEAGIPV RRVRATHAFH TSAMDPMLGQ FQEFLSRQQL RPPRTPLLSN LTGSWMSDQQ
VVDPASWTRQ ISSPIRFADE LDVVLAAPSR ILVEVGPGGS LTGSAMRHPK WSTTHRTVRL
MRHPLQDVDD RDTFLRALGE LWSAGVEVDW TPRRPAVPHL VSLPGYPFAR QRHWVEPNHT
VWAQAPGANN GSPAGTADGS TAATVDAARN GESQTEVTLQ RIWSQCLGVS SVDRNANFFD
LGGDSLMAIS IAMAAANEGL TITPQDLYEY PTLASLTAAV DASFASSGLA KPPEAQANPA
VPPNVTYFLD RGLRDTGRCR VPLILRLDPK IGLPDIRAVL TAVVNHHDAL RLHLVGNDGI
WEQHIAAPAE FTGLSNRSVP NGVAAGSPEE RAAVLGILAE LLEDQTDPNA PLAAVHIAAA
HGGPHYLCLA IHAMVTDDSS RQILATDIVT AFGQRLAGEE ITLEPVSTGW REWSLRCAAL
ATHPAALDTR SYWIENSTKA TLWLADALPN AHTAHPPRAD ELTKLSSTLS VEQTSELDDG
RRRFRRSIQT ILLAALGRTI AQTVGEGVVA VELEGEGRSV LRPDVDLRRT VGWFTTYYPV
PLACATGLGA LAQLDAVHNT LKSVPHYGIG YGLLRYVYAP TGRVLGAQRT PDIHFRYAGV
IPELPSGDAP VQFDSDMTLP VREPIPGMGH AIELRVYRFG GSLHLDWWYD TRRIPAATAE
ALERTFPLAL SALIQEAIAA EHTEHDDSEI VGEPEAGALV DLSSMDAG
