UniProtKB - P9WQ59 (FAA28_MYCTU)
Protein
Long-chain-fatty-acid--AMP ligase FadD28
Gene
fadD28
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Functioni
Involved in the biosynthesis of phthiocerol dimycocerosate (PDIM), a cell wall-associated lipid found only in pathogenic mycobacteria (PubMed:10573420, PubMed:11279114). Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase Mas for further chain extension (PubMed:24831705). Probably plays a role in host phagosome maturation arrest (Probable).1 Publication3 Publications
Catalytic activityi
- a long-chain fatty acid + ATP + holo-[mycocerosate synthase] = AMP + diphosphate + long-chain fatty acyl-[mycocerosate synthase]1 PublicationEC:6.2.1.491 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- a long-chain fatty acyl-AMP + holo-[mycocerosate synthase] = AMP + H+ + long-chain fatty acyl-[mycocerosate synthase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward2 Publications direction.
- This reaction proceeds in the forward1 Publication direction.
Activity regulationi
Inhibited by acylsulfamoyl (acyl-AMS) analogs.1 Publication
: fatty acid biosynthesis Pathwayi
This protein is involved in the pathway fatty acid biosynthesis, which is part of Lipid metabolism.2 PublicationsView all proteins of this organism that are known to be involved in the pathway fatty acid biosynthesis and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 227 | Important for substrate selectivity | 1 | |
Sitei | 330 | Important for substrate selectivity | 1 |
GO - Molecular functioni
- adenylyltransferase activity Source: MTBBASE
- ATP binding Source: UniProtKB-KW
- fatty-acyl-CoA synthase activity Source: MTBBASE
- ligase activity Source: UniProtKB-KW
GO - Biological processi
- DIM/DIP cell wall layer assembly Source: MTBBASE
- fatty acid biosynthetic process Source: GO_Central
- growth of symbiont in host cell Source: MTBBASE
- lipid biosynthetic process Source: MTBBASE
- response to host immune response Source: MTBBASE
- suppression by symbiont of host innate immune response Source: MTBBASE
Keywordsi
Molecular function | Ligase |
Biological process | Fatty acid metabolism, Lipid metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MTU-9635470, Dimycocersyl phthiocerol biosynthesis |
UniPathwayi | UPA00094 |
Chemistry databases
SwissLipidsi | SLP:000000975 |
Names & Taxonomyi
Protein namesi | Recommended name: Long-chain-fatty-acid--AMP ligase FadD28Curated (EC:6.2.1.491 Publication)Alternative name(s): Acyl-AMP synthetase FAAL281 Publication Long-chain fatty acid adenylyltransferase FadD28Curated |
Gene namesi | Name:fadD28 Synonyms:acoas Ordered Locus Names:Rv2941 |
Organismi | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
Taxonomic identifieri | 83332 [NCBI] |
Taxonomic lineagei | Bacteria › Actinobacteria › Corynebacteriales › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex › |
Proteomesi |
|
Organism-specific databases
TubercuListi | Rv2941 |
Pathology & Biotechi
Disruption phenotypei
Disruption of fadD28 abolishes the production of phthiocerol dimycocerosate (DIM) on the cell envelope (PubMed:10573420, PubMed:11279114). Grows normally in liquid culture, traffics into host (human and mouse) acidified compartments early after phagocytosis, suggesting it no longer arrests phagosome maturation as well as wild-type, impaired growth in mouse macrophages (PubMed:20844580).3 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 227 | I → W: Shows substantial decrease (69%) in the activity with lauric acid (C12 fatty acid) as substrate but shows a 4-fold higher activity with the long chain fatty acyl capric acid (C10 fatty acid) as substrate. 1 Publication | 1 | |
Mutagenesisi | 330 | G → W: No activity with lauric acid (C12 fatty acid) as substrate. Instead, it catalyzes activation of acetic acid (C2 fatty acid) as acetyl-AMP. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL5766 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000406355 | 1 – 580 | Long-chain-fatty-acid--AMP ligase FadD28Add BLAST | 580 |
Proteomic databases
PaxDbi | P9WQ59 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P9WQ59 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Belongs to the ATP-dependent AMP-binding enzyme family.Curated
Phylogenomic databases
eggNOGi | COG0318, Bacteria |
OMAi | MLATSSH |
PhylomeDBi | P9WQ59 |
Family and domain databases
Gene3Di | 3.40.50.12780, 1 hit |
InterProi | View protein in InterPro IPR000873, AMP-dep_Synth/Lig IPR042099, AMP-dep_Synthh-like_sf |
Pfami | View protein in Pfam PF00501, AMP-binding, 1 hit |
i Sequence
Sequence statusi: Complete.
P9WQ59-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSVRSLPAAL RACARLQPHD PAFTFMDYEQ DWDGVAITLT WSQLYRRTLN
60 70 80 90 100
VAQELSRCGS TGDRVVISAP QGLEYVVAFL GALQAGRIAV PLSVPQGGVT
110 120 130 140 150
DERSDSVLSD SSPVAILTTS SAVDDVVQHV ARRPGESPPS IIEVDLLDLD
160 170 180 190 200
APNGYTFKED EYPSTAYLQY TSGSTRTPAG VVMSHQNVRV NFEQLMSGYF
210 220 230 240 250
ADTDGIPPPN SALVSWLPFY HDMGLVIGIC APILGGYPAV LTSPVSFLQR
260 270 280 290 300
PARWMHLMAS DFHAFSAAPN FAFELAARRT TDDDMAGRDL GNILTILSGS
310 320 330 340 350
ERVQAATIKR FADRFARFNL QERVIRPSYG LAEATVYVAT SKPGQPPETV
360 370 380 390 400
DFDTESLSAG HAKPCAGGGA TSLISYMLPR SPIVRIVDSD TCIECPDGTV
410 420 430 440 450
GEIWVHGDNV ANGYWQKPDE SERTFGGKIV TPSPGTPEGP WLRTGDSGFV
460 470 480 490 500
TDGKMFIIGR IKDLLIVYGR NHSPDDIEAT IQEITRGRCA AISVPGDRST
510 520 530 540 550
EKLVAIIELK KRGDSDQDAM ARLGAIKREV TSALSSSHGL SVADLVLVAP
560 570 580
GSIPITTSGK VRRGACVEQY RQDQFARLDA
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL123456 Genomic DNA Translation: CCP45744.1 |
PIRi | B70668 |
RefSeqi | NP_217457.1, NC_000962.3 WP_003414857.1, NZ_NVQJ01000015.1 |
Genome annotation databases
EnsemblBacteriai | CCP45744; CCP45744; Rv2941 |
GeneIDi | 23490818 887454 |
KEGGi | mtu:Rv2941 mtv:RVBD_2941 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL123456 Genomic DNA Translation: CCP45744.1 |
PIRi | B70668 |
RefSeqi | NP_217457.1, NC_000962.3 WP_003414857.1, NZ_NVQJ01000015.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3E53 | X-ray | 2.35 | A | 1-460 | [»] | |
3T5A | X-ray | 2.05 | A | 1-460 | [»] | |
SMRi | P9WQ59 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 83332.Rv2941 |
Chemistry databases
ChEMBLi | CHEMBL5766 |
SwissLipidsi | SLP:000000975 |
Proteomic databases
PaxDbi | P9WQ59 |
Genome annotation databases
EnsemblBacteriai | CCP45744; CCP45744; Rv2941 |
GeneIDi | 23490818 887454 |
KEGGi | mtu:Rv2941 mtv:RVBD_2941 |
Organism-specific databases
TubercuListi | Rv2941 |
Phylogenomic databases
eggNOGi | COG0318, Bacteria |
OMAi | MLATSSH |
PhylomeDBi | P9WQ59 |
Enzyme and pathway databases
UniPathwayi | UPA00094 |
Reactomei | R-MTU-9635470, Dimycocersyl phthiocerol biosynthesis |
Miscellaneous databases
PROi | PR:P9WQ59 |
Family and domain databases
Gene3Di | 3.40.50.12780, 1 hit |
InterProi | View protein in InterPro IPR000873, AMP-dep_Synth/Lig IPR042099, AMP-dep_Synthh-like_sf |
Pfami | View protein in Pfam PF00501, AMP-binding, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | FAA28_MYCTU | |
Accessioni | P9WQ59Primary (citable) accession number: P9WQ59 Secondary accession number(s): L0TCP5, P96290, Q7D6E4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2014 |
Last sequence update: | April 16, 2014 | |
Last modified: | December 2, 2020 | |
This is version 33 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families