MALA_MALAU
ID MALA_MALAU Reviewed; 667 AA.
AC L0E155;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Flavin-dependent halogenase malA {ECO:0000303|PubMed:23213353};
DE EC=1.14.-.- {ECO:0000269|PubMed:28777910};
DE AltName: Full=Malbrancheamide biosynthesis cluster protein A {ECO:0000303|PubMed:23213353};
GN Name=malA {ECO:0000303|PubMed:23213353};
OS Malbranchea aurantiaca.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Onygenaceae; Malbranchea.
OX NCBI_TaxID=78605;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=RRC1813;
RX PubMed=23213353; DOI=10.1039/c2md20029e;
RA Li S., Anand K., Tran H., Yu F., Finefield J.M., Sunderhaus J.D.,
RA McAfoos T.J., Tsukamoto S., Williams R.M., Sherman D.H.;
RT "Comparative analysis of the biosynthetic systems for fungal
RT bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(-)-notoamide,
RT paraherquamide and malbrancheamide pathways.";
RL Med. Chem. Commun. 3:987-996(2012).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=18986806; DOI=10.1016/j.bmcl.2008.10.057;
RA Miller K.A., Figueroa M., Valente M.W., Greshock T.J., Mata R.,
RA Williams R.M.;
RT "Calmodulin inhibitory activity of the malbrancheamides and various
RT analogs.";
RL Bioorg. Med. Chem. Lett. 18:6479-6481(2008).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=19185562; DOI=10.1016/j.ab.2009.01.002;
RA Gonzalez-Andrade M., Figueroa M., Rodriguez-Sotres R., Mata R.,
RA Sosa-Peinado A.;
RT "An alternative assay to discover potential calmodulin inhibitors using a
RT human fluorophore-labeled CaM protein.";
RL Anal. Biochem. 387:64-70(2009).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=20939762; DOI=10.3109/14756366.2010.518964;
RA Figueroa M., Gonzalez-Andrade M., Sosa-Peinado A., Madariaga-Mazon A.,
RA Del Rio-Portilla F., Gonzalez M.C., Mata R.;
RT "Fluorescence, circular dichroism, NMR, and docking studies of the
RT interaction of the alkaloid malbrancheamide with calmodulin.";
RL J. Enzym. Inhib. Med. Chem. 26:378-385(2011).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=25643751; DOI=10.1111/jphp.12346;
RA Madariaga-Mazon A., Hernandez-Abreu O., Estrada-Soto S., Mata R.;
RT "Insights on the vasorelaxant mode of action of malbrancheamide.";
RL J. Pharm. Pharmacol. 67:551-558(2015).
RN [6]
RP FUNCTION, AND PATHWAY.
RX PubMed=31548667; DOI=10.1038/s41557-019-0326-6;
RA Dan Q., Newmister S.A., Klas K.R., Fraley A.E., McAfoos T.J., Somoza A.D.,
RA Sunderhaus J.D., Ye Y., Shende V.V., Yu F., Sanders J.N., Brown W.C.,
RA Zhao L., Paton R.S., Houk K.N., Smith J.L., Sherman D.H., Williams R.M.;
RT "Fungal indole alkaloid biogenesis through evolution of a bifunctional
RT reductase/Diels-Alderase.";
RL Nat. Chem. 11:972-980(2019).
RN [7] {ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS, ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU, ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW, ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY, ECO:0007744|PDB:5WGZ}
RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS), CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, MUTAGENESIS OF ASP-109;
RP HIS-253; PHE-489; GLU-494; CYS-613 AND CYS-616, AND DOMAIN.
RX PubMed=28777910; DOI=10.1021/jacs.7b06773;
RA Fraley A.E., Garcia-Borras M., Tripathi A., Khare D., Mercado-Marin E.V.,
RA Tran H., Dan Q., Webb G.P., Watts K.R., Crews P., Sarpong R.,
RA Williams R.M., Smith J.L., Houk K.N., Sherman D.H.;
RT "Function and structure of MalA/MalA', iterative halogenases for late-stage
RT C-H functionalization of indole alkaloids.";
RL J. Am. Chem. Soc. 139:12060-12068(2017).
CC -!- FUNCTION: Flavin-dependent halogenase; part of the gene cluster that
CC mediates the biosynthesis of malbrancheamide, a dichlorinated fungal
CC indole alkaloid that belongs to a family of natural products containing
CC a characteristic bicyclo[2.2.2]diazaoctane core (PubMed:23213353,
CC PubMed:31548667, PubMed:28777910). The first step of malbrancheamide
CC biosynthesis involves coupling of L-proline and L-tryptophan by malG, a
CC bimodular NRPS, to produce L-Pro-L-Trp aldehyde through reductive
CC offloading (PubMed:23213353, PubMed:31548667). This compound undergoes
CC spontaneous cyclization and dehydration to give a dienamine which is
CC reverse prenylated at C-2 by malE (PubMed:31548667). The other
CC prenyltransferase present in the cluster, malB, displays modest
CC activity, suggesting that may be a redundant gene in the pathway
CC (PubMed:31548667). Subsequently, a [4+2] Diels-Alder cyclo-addition
CC catalyzed by the bifunctional enzyme malC forms the characteristic
CC bicyclo[2.2.2]diazaoctane ring of premalbrancheamid (PubMed:31548667).
CC Finally, the flavin-dependent halogenase malA catalyzes the iterative
CC dichlorination of the indole ring of premalbrancheamide to yield C-9
CC monochlorinated malbrancheamide B, C-8 monochlorinated
CC isomalbrancheamide B, and dichlorinated malbrancheamide
CC (PubMed:31548667, PubMed:28777910). MalA is also able to brominate
CC premalbrancheamide at C-9 to yield malbrancheamide C, and, to a lesser
CC extend, at C-8 to yield isomalbrancheamide C (PubMed:28777910).
CC Finally, malA can brominate C-9 monochlorinated malbrancheamide B at C-
CC 8 to yield malbrancheamide D, or C-8 monochlorinated isomalbrancheamide
CC B at C-9 to produce isomalbrancheamide D (PubMed:28777910).
CC {ECO:0000269|PubMed:23213353, ECO:0000269|PubMed:28777910,
CC ECO:0000269|PubMed:31548667}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-premalbrancheamide + 2 chloride + 2 FAD + 4 H(+) = (+)-
CC malbrancheamide + 2 FADH2; Xref=Rhea:RHEA:62296, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17996, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:145651, ChEBI:CHEBI:145658;
CC Evidence={ECO:0000269|PubMed:28777910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62297;
CC Evidence={ECO:0000269|PubMed:28777910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-premalbrancheamide + chloride + FAD + 2 H(+) = (+)-
CC malbrancheamide B + FADH2; Xref=Rhea:RHEA:62308, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17996, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:145658, ChEBI:CHEBI:145677;
CC Evidence={ECO:0000269|PubMed:28777910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62309;
CC Evidence={ECO:0000269|PubMed:28777910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-premalbrancheamide + chloride + FAD + 2 H(+) = (+)-
CC isomalbrancheamide B + FADH2; Xref=Rhea:RHEA:62320,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17996, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:145658, ChEBI:CHEBI:145678;
CC Evidence={ECO:0000269|PubMed:28777910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62321;
CC Evidence={ECO:0000269|PubMed:28777910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-malbrancheamide B + chloride + FAD + 2 H(+) = (+)-
CC malbrancheamide + FADH2; Xref=Rhea:RHEA:62324, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17996, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:145651, ChEBI:CHEBI:145677;
CC Evidence={ECO:0000269|PubMed:28777910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62325;
CC Evidence={ECO:0000269|PubMed:28777910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-isomalbrancheamide B + chloride + FAD + 2 H(+) = (+)-
CC malbrancheamide + FADH2; Xref=Rhea:RHEA:62328, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17996, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:145651, ChEBI:CHEBI:145678;
CC Evidence={ECO:0000269|PubMed:28777910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62329;
CC Evidence={ECO:0000269|PubMed:28777910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-premalbrancheamide + bromide + FAD + 2 H(+) = (+)-
CC malbrancheamide C + FADH2; Xref=Rhea:RHEA:62340, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15858, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:145658, ChEBI:CHEBI:145679;
CC Evidence={ECO:0000269|PubMed:28777910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62341;
CC Evidence={ECO:0000269|PubMed:28777910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-premalbrancheamide + bromide + FAD + 2 H(+) = (+)-
CC isomalbrancheamide C + FADH2; Xref=Rhea:RHEA:62724,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15858, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:145658, ChEBI:CHEBI:145680;
CC Evidence={ECO:0000269|PubMed:28777910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62725;
CC Evidence={ECO:0000269|PubMed:28777910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-malbrancheamide B + bromide + FAD + 2 H(+) = (+)-
CC malbrancheamide D + FADH2; Xref=Rhea:RHEA:62728, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15858, ChEBI:CHEBI:57692, ChEBI:CHEBI:58307,
CC ChEBI:CHEBI:145677, ChEBI:CHEBI:145929;
CC Evidence={ECO:0000269|PubMed:28777910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62729;
CC Evidence={ECO:0000269|PubMed:28777910};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-isomalbrancheamide B + bromide + FAD + 2 H(+) = (+)-
CC isomalbrancheamide D + FADH2; Xref=Rhea:RHEA:62732,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15858, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:145678, ChEBI:CHEBI:145930;
CC Evidence={ECO:0000269|PubMed:28777910};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62733;
CC Evidence={ECO:0000269|PubMed:28777910};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:28777910};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:28777910};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.0 uM for premalbrancheamide (to yield malbrancheamide B)
CC {ECO:0000269|PubMed:28777910};
CC KM=7.5 uM for premalbrancheamide (to yield isomalbrancheamide B)
CC {ECO:0000269|PubMed:28777910};
CC KM=4.4 uM for malbrancheamide B (to yield malbrancheamide)
CC {ECO:0000269|PubMed:28777910};
CC KM=4.0 uM for isomalbrancheamide B (to yield malbrancheamide)
CC {ECO:0000269|PubMed:28777910};
CC Note=The catalytic efficiencies were calculated for each of the four
CC reactions, resulting in the kcat/Km values of 11.5, 12.0, 27.3, and
CC 29.7 min(-1) mM(-1), respectively. {ECO:0000269|PubMed:28777910};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:28777910}.
CC -!- DOMAIN: The very flexible region (621-646) acts as a substrate channel
CC lid, having two main open/closed conformations.
CC {ECO:0000269|PubMed:28777910}.
CC -!- BIOTECHNOLOGY: Malbrancheamides have the ability to inhibit calmodulin,
CC calmodulin-dependent phosphodiesterase (PDE1), and induce both
CC endothelium-independent and endothelium-dependent relaxant effects,
CC suggesting their potential as vasorelaxant agents.
CC {ECO:0000269|PubMed:18986806, ECO:0000269|PubMed:19185562,
CC ECO:0000269|PubMed:20939762, ECO:0000269|PubMed:25643751}.
CC -!- SIMILARITY: Belongs to the flavin-dependent halogenase family.
CC {ECO:0000305}.
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DR EMBL; JQ708193; AGA37261.1; -; Genomic_DNA.
DR PDB; 5WGR; X-ray; 2.36 A; A=1-667.
DR PDB; 5WGS; X-ray; 2.34 A; A=1-667.
DR PDB; 5WGT; X-ray; 2.09 A; A=1-667.
DR PDB; 5WGU; X-ray; 2.05 A; A=1-667.
DR PDB; 5WGV; X-ray; 2.30 A; A=1-667.
DR PDB; 5WGW; X-ray; 2.09 A; A=1-667.
DR PDB; 5WGX; X-ray; 1.97 A; A=1-667.
DR PDB; 5WGY; X-ray; 2.00 A; A=1-667.
DR PDB; 5WGZ; X-ray; 2.04 A; A=1-667.
DR PDBsum; 5WGR; -.
DR PDBsum; 5WGS; -.
DR PDBsum; 5WGT; -.
DR PDBsum; 5WGU; -.
DR PDBsum; 5WGV; -.
DR PDBsum; 5WGW; -.
DR PDBsum; 5WGX; -.
DR PDBsum; 5WGY; -.
DR PDBsum; 5WGZ; -.
DR AlphaFoldDB; L0E155; -.
DR SMR; L0E155; -.
DR BioCyc; MetaCyc:MON-21926; -.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR006905; Flavin_halogenase.
DR Pfam; PF04820; Trp_halogenase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW 3D-structure; FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Zinc.
FT CHAIN 1..667
FT /note="Flavin-dependent halogenase malA"
FT /id="PRO_0000448773"
FT REGION 621..646
FT /note="Flexible region"
FT /evidence="ECO:0000269|PubMed:28777910"
FT ACT_SITE 108
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 70
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 79
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 82
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 144
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 168
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 399
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 412
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 494
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 597
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 600
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 613
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT BINDING 616
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:28777910,
FT ECO:0007744|PDB:5WGR, ECO:0007744|PDB:5WGS,
FT ECO:0007744|PDB:5WGT, ECO:0007744|PDB:5WGU,
FT ECO:0007744|PDB:5WGV, ECO:0007744|PDB:5WGW,
FT ECO:0007744|PDB:5WGX, ECO:0007744|PDB:5WGY,
FT ECO:0007744|PDB:5WGZ"
FT MUTAGEN 109
FT /note="D->A: Leads to very low malA catalytic activity."
FT /evidence="ECO:0000269|PubMed:28777910"
FT MUTAGEN 253
FT /note="H->A: Displays selectivity for producing the C-9-
FT chlorinated malbrancheamide B but does not affect the
FT selectivity for bromination."
FT /evidence="ECO:0000269|PubMed:28777910"
FT MUTAGEN 253
FT /note="H->F: Displays selectivity for producing the C-8-
FT chlorinated isomalbrancheamide B but does not affect the
FT selectivity for bromination."
FT /evidence="ECO:0000269|PubMed:28777910"
FT MUTAGEN 489
FT /note="F->H: Decreases malA catalytic activity."
FT /evidence="ECO:0000269|PubMed:28777910"
FT MUTAGEN 494
FT /note="E->A,Q: Abolishes malA catalytic activity."
FT /evidence="ECO:0000269|PubMed:28777910"
FT MUTAGEN 494
FT /note="E->D: Decreases but maintains slight catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:28777910"
FT MUTAGEN 613
FT /note="C->S: Leads to an insoluble protein; when associated
FT with S-616."
FT /evidence="ECO:0000269|PubMed:28777910"
FT MUTAGEN 616
FT /note="C->S: Leads to an insoluble protein; when associated
FT with S-613."
FT /evidence="ECO:0000269|PubMed:28777910"
FT HELIX 8..16
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 20..25
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 47..59
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 85..93
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 98..104
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:5WGX"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 144..156
FT /evidence="ECO:0007829|PDB:5WGX"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:5WGX"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 182..189
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 196..205
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 228..236
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 253..259
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 262..271
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 277..293
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 303..310
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 315..325
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 335..337
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 341..350
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 354..360
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 375..380
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 410..413
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 416..435
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 438..473
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 479..482
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 484..492
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 497..499
FT /evidence="ECO:0007829|PDB:5WGX"
FT TURN 502..504
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 505..510
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 519..532
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 543..563
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 570..573
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 579..581
FT /evidence="ECO:0007829|PDB:5WGS"
FT STRAND 594..596
FT /evidence="ECO:0007829|PDB:5WGX"
FT TURN 598..600
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 603..605
FT /evidence="ECO:0007829|PDB:5WGX"
FT TURN 614..616
FT /evidence="ECO:0007829|PDB:5WGX"
FT HELIX 623..625
FT /evidence="ECO:0007829|PDB:5WGU"
FT HELIX 635..644
FT /evidence="ECO:0007829|PDB:5WGX"
FT STRAND 653..655
FT /evidence="ECO:0007829|PDB:5WGZ"
SQ SEQUENCE 667 AA; 74698 MW; C1948F84DFCE3B85 CRC64;
MAPTPKYTFT ERAAAGNLSD AEILNSNNPT GSELPDESDV VVGGAGIHGL IYALHASKYK
PNNLKISVIE KNTRPGYKIG ESTLPIFYTW CKLHGISAAY LLRLFGLKDG LCFYFLDREN
QGQYTDFCSV GAPGLVLASL QIERPMSELL FTILAQRNGV NVYHGREVDF KSTVVQGGGQ
GNKIAVSRGK YDSTPKTIDS ALFVDATGRF RQFCSKKAPR HRFDGWNCNA FWGYFTAPKD
ESKIPFDLYE GDHTNHLCFP EGWVWVIRLP SWEGSLIANL MDMVTYILEC ADAGVPGDEL
PSSEELARMF GLKFQWVTSI GFAVRNDVKY PEDLSAYGTR EAEQKFNYFV QKYELLQQFM
SNFELIENLY GPGTTWFIRK TLAYQSPVVS GPGWLAIGDA CGFTNPLYSP GINVGMSTST
WAAQLSHRIV EIGKSAPADA AESSIRKLLV PYDDYCKSLV PALEQMNRFN YVCYRDTRLG
PQVACLWQFF AGIERYLSDV NIETFAHYAI KWVWGAMVPE YQQVAQKCIE HIETVPLDER
LPDAMVDELL AFSNRIKSAA VAADDFSLRW DAILRSFDRS LNFVEGKTSR DIYTRQCSGC
GAWLQLRPDW KKCHSCGLLG TEPQTAVTFD PPLTAEEEAL LYAAWNTAPK YDPSKELKLP
TPTRPAA
