FAA28_MYCTU
ID FAA28_MYCTU Reviewed; 580 AA.
AC P9WQ59; L0TCP5; P96290; Q7D6E4;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Long-chain-fatty-acid--AMP ligase FadD28 {ECO:0000305};
DE EC=6.2.1.49 {ECO:0000269|PubMed:24831705};
DE AltName: Full=Acyl-AMP synthetase;
DE AltName: Full=FAAL28 {ECO:0000303|PubMed:19182784};
DE AltName: Full=Long-chain fatty acid adenylyltransferase FadD28 {ECO:0000305};
GN Name=fadD28; Synonyms=acoas; OrderedLocusNames=Rv2941;
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 FUNCTION IN THE BIOSYNTHESIS OF MYCOCEROSATES, PATHWAY, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10573420; DOI=10.1038/47042;
RA Cox J.S., Chen B., McNeil M., Jacobs W.R. Jr.;
RT "Complex lipid determines tissue-specific replication of Mycobacterium
RT tuberculosis in mice.";
RL Nature 402:79-83(1999).
RN [3]
RP FUNCTION IN THE BIOSYNTHESIS OF MYCOCEROSATES, PATHWAY, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11279114; DOI=10.1074/jbc.m100662200;
RA Camacho L.R., Constant P., Raynaud C., Laneelle M.A., Triccas J.A.,
RA Gicquel B., Daffe M., Guilhot C.;
RT "Analysis of the phthiocerol dimycocerosate locus of Mycobacterium
RT tuberculosis. Evidence that this lipid is involved in the cell wall
RT permeability barrier.";
RL J. Biol. Chem. 276:19845-19854(2001).
RN [4]
RP FUNCTION AS AN ACYL-AMP SYNTHETASE, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15042094; DOI=10.1038/nature02384;
RA Trivedi O.A., Arora P., Sridharan V., Tickoo R., Mohanty D., Gokhale R.S.;
RT "Enzymic activation and transfer of fatty acids as acyl-adenylates in
RT mycobacteria.";
RL Nature 428:441-445(2004).
RN [5]
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 [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Beijing GC1237;
RX PubMed=20844580; DOI=10.1371/journal.ppat.1001100;
RA Brodin P., Poquet Y., Levillain F., Peguillet I., Larrouy-Maumus G.,
RA Gilleron M., Ewann F., Christophe T., Fenistein D., Jang J., Jang M.S.,
RA Park S.J., Rauzier J., Carralot J.P., Shrimpton R., Genovesio A.,
RA Gonzalo-Asensio J.A., Puzo G., Martin C., Brosch R., Stewart G.R.,
RA Gicquel B., Neyrolles O.;
RT "High content phenotypic cell-based visual screen identifies Mycobacterium
RT tuberculosis acyltrehalose-containing glycolipids involved in phagosome
RT remodeling.";
RL PLoS Pathog. 6:E1001100-E1001100(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [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).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24831705; DOI=10.1016/j.ymben.2014.05.002;
RA Menendez-Bravo S., Comba S., Sabatini M., Arabolaza A., Gramajo H.;
RT "Expanding the chemical diversity of natural esters by engineering a
RT polyketide-derived pathway into Escherichia coli.";
RL Metab. Eng. 24:97-106(2014).
RN [9]
RP CRYSTALLIZATION OF THE N-TERMINAL DOMAIN.
RX PubMed=16582482; DOI=10.1107/s1744309106005938;
RA Goyal A., Yousuf M., Rajakumara E., Arora P., Gokhale R.S.,
RA Sankaranarayanan R.;
RT "Crystallization and preliminary X-ray crystallographic studies of the N-
RT terminal domain of FadD28, a fatty-acyl AMP ligase from Mycobacterium
RT tuberculosis.";
RL Acta Crystallogr. F 62:350-352(2006).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-460, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, AND NOMENCLATURE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19182784; DOI=10.1038/nchembio.143;
RA Arora P., Goyal A., Natarajan V.T., Rajakumara E., Verma P., Gupta R.,
RA Yousuf M., Trivedi O.A., Mohanty D., Tyagi A., Sankaranarayanan R.,
RA Gokhale R.S.;
RT "Mechanistic and functional insights into fatty acid activation in
RT Mycobacterium tuberculosis.";
RL Nat. Chem. Biol. 5:166-173(2009).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 1-460 OF MUTANT TRP-330,
RP MUTAGENESIS OF ILE-227 AND GLY-330, AND SUBSTRATE SELECTIVITY.
RX PubMed=22206988; DOI=10.1016/j.jmb.2011.12.031;
RA Goyal A., Verma P., Anandhakrishnan M., Gokhale R.S., Sankaranarayanan R.;
RT "Molecular basis of the functional divergence of fatty acyl-AMP ligase
RT biosynthetic enzymes of Mycobacterium tuberculosis.";
RL J. Mol. Biol. 416:221-238(2012).
CC -!- FUNCTION: Involved in the biosynthesis of phthiocerol dimycocerosate
CC (PDIM), a cell wall-associated lipid found only in pathogenic
CC mycobacteria (PubMed:10573420, PubMed:11279114). Catalyzes the
CC activation of long-chain fatty acids as acyl-adenylates (acyl-AMP),
CC which are then transferred to the multifunctional polyketide synthase
CC Mas for further chain extension (PubMed:24831705). Probably plays a
CC role in host phagosome maturation arrest (Probable).
CC {ECO:0000269|PubMed:10573420, ECO:0000269|PubMed:11279114,
CC ECO:0000269|PubMed:24831705, ECO:0000305|PubMed:20844580}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acid + ATP + holo-[mycocerosate synthase] =
CC AMP + diphosphate + long-chain fatty acyl-[mycocerosate synthase];
CC Xref=Rhea:RHEA:10696, Rhea:RHEA-COMP:12641, Rhea:RHEA-COMP:13239,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57560,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:133243, ChEBI:CHEBI:456215;
CC EC=6.2.1.49; Evidence={ECO:0000269|PubMed:24831705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10697;
CC Evidence={ECO:0000269|PubMed:24831705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acid + ATP + H(+) = a long-chain fatty
CC acyl-AMP + diphosphate; Xref=Rhea:RHEA:52336, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57560,
CC ChEBI:CHEBI:136562; Evidence={ECO:0000269|PubMed:24831705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52337;
CC Evidence={ECO:0000269|PubMed:24831705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acyl-AMP + holo-[mycocerosate synthase] =
CC AMP + H(+) + long-chain fatty acyl-[mycocerosate synthase];
CC Xref=Rhea:RHEA:52340, Rhea:RHEA-COMP:12641, Rhea:RHEA-COMP:13239,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64479, ChEBI:CHEBI:133243,
CC ChEBI:CHEBI:136562, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:24831705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52341;
CC Evidence={ECO:0000269|PubMed:24831705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dodecanoate + H(+) = diphosphate + dodecanoyl-AMP;
CC Xref=Rhea:RHEA:43712, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:83623;
CC Evidence={ECO:0000269|PubMed:15042094, ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43713;
CC Evidence={ECO:0000269|PubMed:15042094, ECO:0000269|PubMed:19182784};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H(+) + hexadecanoate = diphosphate + hexadecanoyl-AMP;
CC Xref=Rhea:RHEA:43708, ChEBI:CHEBI:7896, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:83627;
CC Evidence={ECO:0000269|PubMed:19182784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43709;
CC Evidence={ECO:0000269|PubMed:19182784};
CC -!- ACTIVITY REGULATION: Inhibited by acylsulfamoyl (acyl-AMS) analogs.
CC {ECO:0000269|PubMed:19182784}.
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:10573420, ECO:0000269|PubMed:11279114}.
CC -!- DISRUPTION PHENOTYPE: Disruption of fadD28 abolishes the production of
CC phthiocerol dimycocerosate (DIM) on the cell envelope (PubMed:10573420,
CC PubMed:11279114). Grows normally in liquid culture, traffics into host
CC (human and mouse) acidified compartments early after phagocytosis,
CC suggesting it no longer arrests phagosome maturation as well as wild-
CC type, impaired growth in mouse macrophages (PubMed:20844580).
CC {ECO:0000269|PubMed:10573420, ECO:0000269|PubMed:11279114,
CC ECO:0000269|PubMed:20844580}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP45744.1; -; Genomic_DNA.
DR PIR; B70668; B70668.
DR RefSeq; NP_217457.1; NC_000962.3.
DR RefSeq; WP_003414857.1; NZ_NVQJ01000015.1.
DR PDB; 3E53; X-ray; 2.35 A; A=1-460.
DR PDB; 3T5A; X-ray; 2.05 A; A=1-460.
DR PDBsum; 3E53; -.
DR PDBsum; 3T5A; -.
DR AlphaFoldDB; P9WQ59; -.
DR SMR; P9WQ59; -.
DR STRING; 83332.Rv2941; -.
DR BindingDB; P9WQ59; -.
DR ChEMBL; CHEMBL5766; -.
DR SwissLipids; SLP:000000975; -.
DR PaxDb; P9WQ59; -.
DR DNASU; 887454; -.
DR GeneID; 887454; -.
DR KEGG; mtu:Rv2941; -.
DR TubercuList; Rv2941; -.
DR eggNOG; COG0318; Bacteria.
DR OMA; MLATSSH; -.
DR PhylomeDB; P9WQ59; -.
DR BRENDA; 6.2.1.49; 3445.
DR Reactome; R-MTU-9635470; Dimycocersyl phthiocerol biosynthesis.
DR UniPathway; UPA00094; -.
DR PRO; PR:P9WQ59; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0070566; F:adenylyltransferase activity; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004321; F:fatty-acyl-CoA synthase activity; IDA:MTBBASE.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0071770; P:DIM/DIP cell wall layer assembly; IMP:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IMP:MTBBASE.
DR GO; GO:0052170; P:suppression by symbiont of host innate immune response; IDA:MTBBASE.
DR CDD; cd05931; FAAL; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR040097; FAAL/FAAC.
DR Pfam; PF00501; AMP-binding; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Fatty acid metabolism; Ligase; Lipid metabolism;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..580
FT /note="Long-chain-fatty-acid--AMP ligase FadD28"
FT /id="PRO_0000406355"
FT REGION 421..440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 227
FT /note="Important for substrate selectivity"
FT SITE 330
FT /note="Important for substrate selectivity"
FT MUTAGEN 227
FT /note="I->W: Shows substantial decrease (69%) in the
FT activity with lauric acid (C12 fatty acid) as substrate but
FT shows a 4-fold higher activity with the long chain fatty
FT acyl capric acid (C10 fatty acid) as substrate."
FT /evidence="ECO:0000269|PubMed:22206988"
FT MUTAGEN 330
FT /note="G->W: No activity with lauric acid (C12 fatty acid)
FT as substrate. Instead, it catalyzes activation of acetic
FT acid (C2 fatty acid) as acetyl-AMP."
FT /evidence="ECO:0000269|PubMed:22206988"
FT HELIX 6..16
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 20..27
FT /evidence="ECO:0007829|PDB:3T5A"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 41..55
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 73..84
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 103..111
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 114..118
FT /evidence="ECO:0007829|PDB:3T5A"
FT TURN 120..122
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 123..128
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 140..143
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 164..169
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 185..199
FT /evidence="ECO:0007829|PDB:3T5A"
FT TURN 201..205
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 211..215
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 224..228
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 230..235
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 244..249
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 252..257
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 260..268
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 270..279
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 295..298
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:3E53"
FT HELIX 305..314
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:3T5A"
FT TURN 332..335
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 336..340
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 354..358
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 371..374
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 380..387
FT /evidence="ECO:0007829|PDB:3T5A"
FT TURN 389..391
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 401..407
FT /evidence="ECO:0007829|PDB:3T5A"
FT HELIX 418..425
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 441..451
FT /evidence="ECO:0007829|PDB:3T5A"
FT STRAND 454..459
FT /evidence="ECO:0007829|PDB:3T5A"
SQ SEQUENCE 580 AA; 62641 MW; 60842A083746AFD3 CRC64;
MSVRSLPAAL RACARLQPHD PAFTFMDYEQ DWDGVAITLT WSQLYRRTLN VAQELSRCGS
TGDRVVISAP QGLEYVVAFL GALQAGRIAV PLSVPQGGVT DERSDSVLSD SSPVAILTTS
SAVDDVVQHV ARRPGESPPS IIEVDLLDLD APNGYTFKED EYPSTAYLQY TSGSTRTPAG
VVMSHQNVRV NFEQLMSGYF ADTDGIPPPN SALVSWLPFY HDMGLVIGIC APILGGYPAV
LTSPVSFLQR PARWMHLMAS DFHAFSAAPN FAFELAARRT TDDDMAGRDL GNILTILSGS
ERVQAATIKR FADRFARFNL QERVIRPSYG LAEATVYVAT SKPGQPPETV DFDTESLSAG
HAKPCAGGGA TSLISYMLPR SPIVRIVDSD TCIECPDGTV GEIWVHGDNV ANGYWQKPDE
SERTFGGKIV TPSPGTPEGP WLRTGDSGFV TDGKMFIIGR IKDLLIVYGR NHSPDDIEAT
IQEITRGRCA AISVPGDRST EKLVAIIELK KRGDSDQDAM ARLGAIKREV TSALSSSHGL
SVADLVLVAP GSIPITTSGK VRRGACVEQY RQDQFARLDA
