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Protein

Flavin-dependent tryptophan halogenase RebH

Gene

rebH

Organism
Lechevalieria aerocolonigenes (Nocardia aerocolonigenes) (Saccharothrix aerocolonigenes)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the biosynthesis of the indolocarbazole antitumor agent rebeccamycin. Catalyze the chlorination of tryptophan (Trp) at C7 position to yield 7-chlorotryptophan. The reaction between FADH2, Cl-, and O2 generates the powerful oxidant HOCl, which is presumed to carry out the chlorination reaction. The reaction of HOCl with the active site Lys-79 generates a lysine chloramine, which plays a key role in directing regiospecific chlorination of substrate in this important class of biosynthetic enzymes. It is also able to use bromide ions to generate monobrominated Trp.3 Publications

Catalytic activityi

Tryptophan + FADH2 + chloride + O2 + H+ = 7-chloro-L-tryptophan + FAD + 2 H2O.2 Publications

Cofactori

FAD3 Publications

Kineticsi

Kcat for tryptophan is 1.4 (min-1).

  1. KM=2 µM for tryptophan (with FAD)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei791 Publication1
    Binding sitei197FAD; via amide nitrogen and carbonyl oxygen2 Publications1
    Binding sitei348FAD2 Publications1
    Binding sitei357L-tryptophan; via carbonyl oxygen1
    Binding sitei360Chloride; via amide nitrogen1
    Binding sitei361FAD; via amide nitrogen2 Publications1
    Binding sitei461L-tryptophan1
    Binding sitei465L-tryptophan; via carbonyl oxygen1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi13 – 16FAD2 Publications4
    Nucleotide bindingi39 – 41FAD2 Publications3
    Nucleotide bindingi49 – 50FAD2 Publications2

    GO - Molecular functioni

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    FAD, Flavoprotein, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15085.
    BRENDAi1.14.14.7. 4340.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Flavin-dependent tryptophan halogenase RebH (EC:1.14.19.9)
    Gene namesi
    Name:rebH
    Synonyms:rbmJ
    OrganismiLechevalieria aerocolonigenes (Nocardia aerocolonigenes) (Saccharothrix aerocolonigenes)
    Taxonomic identifieri68170 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaPseudonocardialesPseudonocardiaceaeLechevalieria

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi79K → A: Complete loss of halogenase activity. 1 Publication1
    Mutagenesisi79K → M: Complete loss of halogenase activity. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00004223341 – 530Flavin-dependent tryptophan halogenase RebHAdd BLAST530

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Structurei

    Secondary structure

    1530
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi7 – 11Combined sources5
    Helixi15 – 27Combined sources13
    Turni28 – 30Combined sources3
    Beta strandi31 – 38Combined sources8
    Helixi54 – 58Combined sources5
    Helixi60 – 63Combined sources4
    Helixi67 – 73Combined sources7
    Beta strandi77 – 79Combined sources3
    Beta strandi81 – 89Combined sources9
    Beta strandi103 – 112Combined sources10
    Beta strandi116 – 121Combined sources6
    Helixi122 – 131Combined sources10
    Helixi139 – 143Combined sources5
    Helixi146 – 151Combined sources6
    Beta strandi168 – 171Combined sources4
    Helixi173 – 187Combined sources15
    Beta strandi191 – 194Combined sources4
    Beta strandi197 – 202Combined sources6
    Beta strandi208 – 213Combined sources6
    Beta strandi218 – 220Combined sources3
    Beta strandi222 – 226Combined sources5
    Helixi229 – 231Combined sources3
    Helixi233 – 238Combined sources6
    Beta strandi243 – 245Combined sources3
    Turni247 – 249Combined sources3
    Beta strandi254 – 261Combined sources8
    Helixi264 – 267Combined sources4
    Beta strandi271 – 277Combined sources7
    Beta strandi279 – 287Combined sources9
    Beta strandi289 – 298Combined sources10
    Turni300 – 302Combined sources3
    Helixi305 – 315Combined sources11
    Turni320 – 322Combined sources3
    Beta strandi326 – 329Combined sources4
    Beta strandi333 – 336Combined sources4
    Beta strandi338 – 340Combined sources3
    Beta strandi343 – 345Combined sources3
    Turni348 – 350Combined sources3
    Helixi360 – 373Combined sources14
    Helixi382 – 408Combined sources27
    Helixi416 – 421Combined sources6
    Helixi428 – 438Combined sources11
    Beta strandi447 – 449Combined sources3
    Helixi451 – 456Combined sources6
    Helixi458 – 462Combined sources5
    Helixi468 – 478Combined sources11
    Helixi487 – 491Combined sources5
    Helixi493 – 498Combined sources6
    Helixi500 – 516Combined sources17
    Helixi520 – 527Combined sources8

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2E4GX-ray2.08A/B1-530[»]
    2O9ZX-ray2.49A/B1-530[»]
    2OA1X-ray2.15A/B1-530[»]
    2OALX-ray2.10A/B1-530[»]
    2OAMX-ray2.30A/B1-530[»]
    4LU6X-ray3.05A/B1-530[»]
    ProteinModelPortaliQ8KHZ8.
    SMRiQ8KHZ8.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8KHZ8.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni454 – 455L-tryptophan binding2

    Sequence similaritiesi

    Belongs to the RebH family.Curated

    Phylogenomic databases

    KOiK14266.

    Family and domain databases

    Gene3Di3.50.50.60. 3 hits.
    InterProiIPR023753. FAD/NAD-binding_dom.
    IPR006905. Flavin_halogenase.
    IPR033856. Trp_halogen.
    [Graphical view]
    PfamiPF04820. Trp_halogenase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF011396. Trp_halogenase. 1 hit.
    SUPFAMiSSF51905. SSF51905. 3 hits.

    Sequencei

    Sequence statusi: Complete.

    Q8KHZ8-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSGKIDKILI VGGGTAGWMA ASYLGKALQG TADITLLQAP DIPTLGVGEA
    60 70 80 90 100
    TIPNLQTAFF DFLGIPEDEW MRECNASYKV AIKFINWRTA GEGTSEAREL
    110 120 130 140 150
    DGGPDHFYHS FGLLKYHEQI PLSHYWFDRS YRGKTVEPFD YACYKEPVIL
    160 170 180 190 200
    DANRSPRRLD GSKVTNYAWH FDAHLVADFL RRFATEKLGV RHVEDRVEHV
    210 220 230 240 250
    QRDANGNIES VRTATGRVFD ADLFVDCSGF RGLLINKAME EPFLDMSDHL
    260 270 280 290 300
    LNDSAVATQV PHDDDANGVE PFTSAIAMKS GWTWKIPMLG RFGTGYVYSS
    310 320 330 340 350
    RFATEDEAVR EFCEMWHLDP ETQPLNRIRF RVGRNRRAWV GNCVSIGTSS
    360 370 380 390 400
    CFVEPLESTG IYFVYAALYQ LVKHFPDKSL NPVLTARFNR EIETMFDDTR
    410 420 430 440 450
    DFIQAHFYFS PRTDTPFWRA NKELRLADGM QEKIDMYRAG MAINAPASDD
    460 470 480 490 500
    AQLYYGNFEE EFRNFWNNSN YYCVLAGLGL VPDAPSPRLA HMPQATESVD
    510 520 530
    EVFGAVKDRQ RNLLETLPSL HEFLRQQHGR
    Length:530
    Mass (Da):60,297
    Last modified:October 1, 2002 - v1
    Checksum:i41825423F03151AB
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF534707 Genomic DNA. Translation: AAN01216.1.
    AB090952 Genomic DNA. Translation: BAC10682.1.
    AB071405 Genomic DNA. Translation: BAC15758.1.
    AJ414559 Genomic DNA. Translation: CAC93722.1.

    Genome annotation databases

    KEGGiag:BAC10682.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF534707 Genomic DNA. Translation: AAN01216.1.
    AB090952 Genomic DNA. Translation: BAC10682.1.
    AB071405 Genomic DNA. Translation: BAC15758.1.
    AJ414559 Genomic DNA. Translation: CAC93722.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2E4GX-ray2.08A/B1-530[»]
    2O9ZX-ray2.49A/B1-530[»]
    2OA1X-ray2.15A/B1-530[»]
    2OALX-ray2.10A/B1-530[»]
    2OAMX-ray2.30A/B1-530[»]
    4LU6X-ray3.05A/B1-530[»]
    ProteinModelPortaliQ8KHZ8.
    SMRiQ8KHZ8.
    ModBaseiSearch...
    MobiDBiSearch...

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    KEGGiag:BAC10682.

    Phylogenomic databases

    KOiK14266.

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15085.
    BRENDAi1.14.14.7. 4340.

    Miscellaneous databases

    EvolutionaryTraceiQ8KHZ8.

    Family and domain databases

    Gene3Di3.50.50.60. 3 hits.
    InterProiIPR023753. FAD/NAD-binding_dom.
    IPR006905. Flavin_halogenase.
    IPR033856. Trp_halogen.
    [Graphical view]
    PfamiPF04820. Trp_halogenase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF011396. Trp_halogenase. 1 hit.
    SUPFAMiSSF51905. SSF51905. 3 hits.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiREBH_NOCAE
    AccessioniPrimary (citable) accession number: Q8KHZ8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 29, 2013
    Last sequence update: October 1, 2002
    Last modified: November 30, 2016
    This is version 60 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.