FAA32_MYCS2
ID FAA32_MYCS2 Reviewed; 630 AA.
AC A0R618; I7GFQ6;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Long-chain-fatty-acid--AMP ligase FadD32 {ECO:0000305};
DE Short=FAAL {ECO:0000305};
DE EC=6.2.1.20 {ECO:0000250|UniProtKB:O53580};
DE AltName: Full=Acyl-AMP synthetase {ECO:0000305};
GN Name=fadD32 {ECO:0000312|EMBL:AFP42651.1};
GN OrderedLocusNames=MSMEG_6393 {ECO:0000312|EMBL:ABK74035.1},
GN MSMEI_6225 {ECO:0000312|EMBL:AFP42651.1};
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=23364516; DOI=10.1177/1087057112474691;
RA Galandrin S., Guillet V., Rane R.S., Leger M., N R., Eynard N., Das K.,
RA Balganesh T.S., Mourey L., Daffe M., Marrakchi H.;
RT "Assay development for identifying inhibitors of the mycobacterial FadD32
RT activity.";
RL J. Biomol. Screen. 18:576-587(2013).
RN [5] {ECO:0007744|PDB:5D6J, ECO:0007744|PDB:5D6N}
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN APO FORM AND IN COMPLEX WITH ATP,
RP AND DOMAIN.
RX PubMed=26628098; DOI=10.1038/srep15493;
RA Li W., Gu S., Fleming J., Bi L.;
RT "Crystal structure of FadD32, an enzyme essential for mycolic acid
RT biosynthesis in mycobacteria.";
RL Sci. Rep. 5:15493-15493(2015).
RN [6] {ECO:0007744|PDB:5EY8}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) IN COMPLEX WITH ALKYL ADENYLATE
RP INHIBITOR AMPC20, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=26900152; DOI=10.1074/jbc.m115.712612;
RA Guillet V., Galandrin S., Maveyraud L., Ladeveze S., Mariaule V., Bon C.,
RA Eynard N., Daffe M., Marrakchi H., Mourey L.;
RT "Insight into structure-function relationships and inhibition of the fatty
RT acyl-AMP ligase (FadD32) orthologs from Mycobacteria.";
RL J. Biol. Chem. 291:7973-7989(2016).
RN [7] {ECO:0007744|PDB:5ICR}
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RG Center for Structural Genomics of Infectious Diseases (CSGID);
RA Minasov G., Shuvalova L., Hung D., Fisher S.L., Edelstein J.,
RA Kiryukhina O., Dubrovska I., Anderson W.F.;
RT "2.25 Angstrom resolution crystal structure of fatty-acid-coa ligase
RT (FadD32) from Mycobacterium smegmatis in complex with inhibitor 5'-O-[(11-
RT phenoxyundecanoyl)sulfamoyl]adenosine.";
RL Submitted (FEB-2016) to the PDB data bank.
CC -!- FUNCTION: Involved in the biosynthesis of mycolic acids (By
CC similarity). Catalyzes the activation of long-chain fatty acids as
CC acyl-adenylates (acyl-AMP), which are then transferred to the
CC phosphopantetheine arm of the polyketide synthase Pks13 for further
CC chain extension (By similarity). Can use decanoate (C10), dodecanoate
CC (C12) and tetradecanoate (C14) (PubMed:23364516, PubMed:26900152).
CC {ECO:0000250|UniProtKB:O53580, ECO:0000269|PubMed:23364516,
CC ECO:0000269|PubMed:26900152}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acid + ATP + holo-[ACP] = a long-chain
CC fatty acyl-[ACP] + AMP + diphosphate; Xref=Rhea:RHEA:45588,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:12682, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57560, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:133243, ChEBI:CHEBI:456215; EC=6.2.1.20;
CC Evidence={ECO:0000250|UniProtKB:O53580};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45589;
CC Evidence={ECO:0000250|UniProtKB:O53580};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + decanoate + H(+) = decanoyl-AMP + diphosphate;
CC Xref=Rhea:RHEA:65008, ChEBI:CHEBI:15378, ChEBI:CHEBI:27689,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:156261;
CC Evidence={ECO:0000269|PubMed:23364516};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65009;
CC Evidence={ECO:0000269|PubMed:23364516};
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:23364516, ECO:0000269|PubMed:26900152};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43713;
CC Evidence={ECO:0000269|PubMed:23364516, ECO:0000269|PubMed:26900152};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H(+) + tetradecanoate = diphosphate + tetradecanoyl-AMP;
CC Xref=Rhea:RHEA:43704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:33019, ChEBI:CHEBI:83626;
CC Evidence={ECO:0000269|PubMed:23364516, ECO:0000269|PubMed:26900152};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43705;
CC Evidence={ECO:0000269|PubMed:23364516, ECO:0000269|PubMed:26900152};
CC -!- ACTIVITY REGULATION: The acyl-AMP ligase activity is inhibited by the
CC alkylphosphate ester of AMP, adenosine 50-dodecylphosphate (AMPC12)
CC (PubMed:23364516, PubMed:26900152). Also inhibited by eicosyl-AMP
CC (AMPC20) (PubMed:26900152). {ECO:0000269|PubMed:23364516,
CC ECO:0000269|PubMed:26900152}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=259.0 uM for decanoate {ECO:0000269|PubMed:23364516};
CC KM=25.9 uM for dodecanoate {ECO:0000269|PubMed:23364516};
CC KM=5.2 uM for tetradecanoate {ECO:0000269|PubMed:23364516};
CC KM=76.0 uM for ATP {ECO:0000269|PubMed:23364516};
CC KM=112 uM for ATP {ECO:0000269|PubMed:26900152};
CC Note=kcat is 16.1 min(-1) with decanoate as substrate
CC (PubMed:23364516). kcat is 11.2 min(-1) with dodecanoate as substrate
CC (PubMed:23364516). kcat is 4.2 min(-1) with tetradecanoate as
CC substrate (PubMed:23364516). {ECO:0000269|PubMed:23364516};
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:23364516};
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000250|UniProtKB:O53580}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:26900152}.
CC -!- DOMAIN: Consists of two globular domains connected by a flexible
CC linker. ATP binds in a cleft at the interface between the N- and C-
CC terminal domains and its binding induces significant local
CC conformational changes. {ECO:0000269|PubMed:26628098}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; CP000480; ABK74035.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP42651.1; -; Genomic_DNA.
DR RefSeq; WP_011731257.1; NZ_SIJM01000013.1.
DR RefSeq; YP_890606.1; NC_008596.1.
DR PDB; 5D6J; X-ray; 2.25 A; A=1-630.
DR PDB; 5D6N; X-ray; 2.40 A; A=1-484.
DR PDB; 5EY8; X-ray; 3.50 A; A/B/C/D/E/F/G/H=1-630.
DR PDB; 5ICR; X-ray; 2.25 A; A/B/C/D=1-630.
DR PDBsum; 5D6J; -.
DR PDBsum; 5D6N; -.
DR PDBsum; 5EY8; -.
DR PDBsum; 5ICR; -.
DR AlphaFoldDB; A0R618; -.
DR SMR; A0R618; -.
DR STRING; 246196.MSMEI_6225; -.
DR PRIDE; A0R618; -.
DR EnsemblBacteria; ABK74035; ABK74035; MSMEG_6393.
DR EnsemblBacteria; AFP42651; AFP42651; MSMEI_6225.
DR GeneID; 66737671; -.
DR KEGG; msg:MSMEI_6225; -.
DR KEGG; msm:MSMEG_6393; -.
DR PATRIC; fig|246196.19.peg.6220; -.
DR eggNOG; COG0318; Bacteria.
DR OMA; NGRNIWP; -.
DR OrthoDB; 572620at2; -.
DR UniPathway; UPA00915; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008922; F:long-chain fatty acid [acyl-carrier-protein] ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0008610; P:lipid biosynthetic process; IEA:InterPro.
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..630
FT /note="Long-chain-fatty-acid--AMP ligase FadD32"
FT /id="PRO_0000451463"
FT BINDING 187..192
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:26628098,
FT ECO:0007744|PDB:5D6J"
FT BINDING 342
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:26628098,
FT ECO:0007744|PDB:5D6J"
FT BINDING 346
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:26628098,
FT ECO:0007744|PDB:5D6J"
FT BINDING 469
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:26628098,
FT ECO:0007744|PDB:5D6J"
FT BINDING 483
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:26628098,
FT ECO:0007744|PDB:5D6J"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:5ICR"
FT HELIX 21..31
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 35..42
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 44..48
FT /evidence="ECO:0007829|PDB:5EY8"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 56..73
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 88..99
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 116..126
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:5D6J"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 138..145
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 164..169
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 201..215
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:5D6N"
FT HELIX 232..238
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 241..244
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 253..258
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 261..267
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 283..292
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 319..329
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 339..344
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 349..354
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:5EY8"
FT STRAND 363..367
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 368..372
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:5EY8"
FT STRAND 386..391
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 399..405
FT /evidence="ECO:0007829|PDB:5D6J"
FT TURN 406..409
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 418..424
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 435..442
FT /evidence="ECO:0007829|PDB:5D6J"
FT TURN 454..457
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 464..474
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 477..483
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 484..486
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 488..490
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 493..495
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 497..507
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 515..522
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 523..525
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 528..532
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 534..536
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 547..554
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 564..579
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 583..589
FT /evidence="ECO:0007829|PDB:5D6J"
FT STRAND 598..600
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 604..611
FT /evidence="ECO:0007829|PDB:5D6J"
FT TURN 612..614
FT /evidence="ECO:0007829|PDB:5D6J"
FT HELIX 615..618
FT /evidence="ECO:0007829|PDB:5D6J"
SQ SEQUENCE 630 AA; 68229 MW; 71627AEAD5FA8772 CRC64;
MPFHNPFIKD GQIKFPDGSS IVAHVERWAK VRGDKLAYRF LDFSTERDGV PRDLTWAQFS
ARNRAVAARL QQVTQPGDRV AILCPQNLDY LVAFFGALYA GRIAVPLFDP SEPGHVGRLH
AVLDNCHPSA ILTTTEAAEG VRKFFRTRPA NQRPRVIAVD AVPDDVASTW VNPDEPDETT
IAYLQYTSGS TRIPTGVQIT HLNLATNVVQ VIEALEGEEG DRGLSWLPFF HDMGLITALL
APMIGHYFTF MTPAAFVRRP ERWIRELARK EGDTGGTISV APNFAFDHAA ARGVPKPGSP
PLDLSNVKAV LNGSEPISAA TVRRFNEAFG PFGFPPKAIK PSYGLAEATL FVSTTPSAEE
PKIITVDRDQ LNSGRIVEVD ADSPKAVAQA SAGKVGIAEW AVIVDAESAT ELPDGQVGEI
WISGQNMGTG YWGKPEESVA TFQNILKSRT NPSHAEGATD DATWVRTGDY GAFYDGDLYI
TGRVKDLVII DGRNHYPQDL EYSAQEASKA IRTGYVAAFS VPANQLPDEV FENAHSGIKR
DPDDTSEQLV IVAERAPGAH KLDIGPITDD IRAAIAVRHG VTVRDVLLTA AGAIPRTSSG
KIGRRACRAA YLDGSLRAGK VANDFPDATD
