MNLOX_GAEAV
ID MNLOX_GAEAV Reviewed; 618 AA.
AC Q8X151;
DT 01-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2016, sequence version 2.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Manganese lipoxygenase {ECO:0000303|PubMed:12047377};
DE Short=Mn-LO {ECO:0000303|PubMed:15629124};
DE Short=MnLOX {ECO:0000303|PubMed:12047377};
DE EC=1.13.11.- {ECO:0000269|PubMed:15629124};
DE EC=1.13.11.45 {ECO:0000269|PubMed:15629124};
DE AltName: Full=Linoleate 11S-lipoxygenase {ECO:0000305|PubMed:9582345};
DE AltName: Full=Linoleate 13R-lipoxygenase {ECO:0000305|PubMed:9582345};
DE AltName: Full=Manganese 13R-lipoxygenase {ECO:0000303|PubMed:23233731};
DE Short=13R-MnLOX {ECO:0000303|PubMed:23233731};
DE Flags: Precursor;
OS Gaeumannomyces avenae (Oat take-all root rot fungus) (Gaeumannomyces
OS graminis var. avenae).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Magnaporthales; Magnaporthaceae; Gaeumannomyces.
OX NCBI_TaxID=36778;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RC STRAIN=CBS 870.73;
RX PubMed=12047377; DOI=10.1046/j.1432-1033.2002.02936.x;
RA Hornsten L., Su C., Osbourn A.E., Hellman U., Oliw E.H.;
RT "Cloning of the manganese lipoxygenase gene reveals homology with the
RT lipoxygenase gene family.";
RL Eur. J. Biochem. 269:2690-2697(2002).
RN [2]
RP SEQUENCE REVISION TO 52 AND 158, AND MUTAGENESIS OF GLY-332; LEU-336 AND
RP PHE-337.
RX PubMed=22822060; DOI=10.1074/jbc.m112.364331;
RA Wennman A., Jerneren F., Hamberg M., Oliw E.H.;
RT "Catalytic convergence of manganese and iron lipoxygenases by replacement
RT of a single amino acid.";
RL J. Biol. Chem. 287:31757-31765(2012).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=9582345; DOI=10.1074/jbc.273.21.13072;
RA Su C., Oliw E.H.;
RT "Manganese lipoxygenase. Purification and characterization.";
RL J. Biol. Chem. 273:13072-13079(1998).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP MUTAGENESIS OF HIS-290; HIS-294; HIS-478; HIS-479; ASN-482; GLN-483 AND
RP VAL-618, AND GLYCOSYLATION.
RX PubMed=15629124; DOI=10.1016/j.abb.2004.10.026;
RA Cristea M., Engstroem K., Su C., Hoernsten L., Oliw E.H.;
RT "Expression of manganese lipoxygenase in Pichia pastoris and site-directed
RT mutagenesis of putative metal ligands.";
RL Arch. Biochem. Biophys. 434:201-211(2005).
RN [5]
RP MUTAGENESIS OF GLY-332.
RX PubMed=16641090; DOI=10.1074/jbc.m510311200;
RA Cristea M., Oliw E.H.;
RT "A G316A mutation of manganese lipoxygenase augments hydroperoxide
RT isomerase activity: mechanism of biosynthesis of epoxyalcohols.";
RL J. Biol. Chem. 281:17612-17623(2006).
RN [6]
RP MUTAGENESIS OF GLY-332; ASN-482 AND SER-485.
RX PubMed=18024999; DOI=10.1194/jlr.m700514-jlr200;
RA Oliw E.H.;
RT "Factors influencing the rearrangement of bis-allylic hydroperoxides by
RT manganese lipoxygenase.";
RL J. Lipid Res. 49:420-428(2008).
RN [7]
RP MUTAGENESIS OF PHE-347.
RX PubMed=23233731; DOI=10.1194/jlr.m033787;
RA Wennman A., Oliw E.H.;
RT "Secretion of two novel enzymes, manganese 9S-lipoxygenase and epoxy
RT alcohol synthase, by the rice pathogen Magnaporthe salvinii.";
RL J. Lipid Res. 54:762-775(2013).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH MANGANESE, AND
RP GLYCOSYLATION AT ASN-60; ASN-91; ASN-106; ASN-116 AND ASN-157.
RX PubMed=27313058; DOI=10.1194/jlr.m069617;
RA Chen Y., Wennman A., Karkehabadi S., Engstroem A., Oliw E.H.;
RT "Crystal structure of linoleate 13R-manganese lipoxygenase in complex with
RT an adhesion protein.";
RL J. Lipid Res. 57:1574-1588(2016).
CC -!- FUNCTION: Lipoxygenase that metabolizes linoleic and alpha-linolenic
CC acids to 11S- and 13R-hydroperoxy fatty acids. At the end of
CC lipoxygenation, the intermediate product 11S-HPODE from linoleic acid
CC is then transformed into 13R-HPODE as the final product. It also acts
CC on alpha-linolenic acid producing 11S-HPOTrE and 13R-HPOTrE with
CC subsequent transformation of 11S-HPOTrE to 13R-HPOTrE as final product.
CC {ECO:0000269|PubMed:15629124}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate + O2 = (11S)-hydroperoxy-(9Z,12Z)-
CC octadecadienoate; Xref=Rhea:RHEA:18993, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:57467; EC=1.13.11.45;
CC Evidence={ECO:0000269|PubMed:15629124};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate + O2 = (13R)-hydroperoxy-(9Z,11E)-
CC octadecadienoate; Xref=Rhea:RHEA:51240, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:133985;
CC Evidence={ECO:0000269|PubMed:15629124};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z,15Z)-octadecatrienoate + O2 = (11S)-hydroperoxy-
CC (9Z,12Z,15Z)-octadecatrienoate; Xref=Rhea:RHEA:51440,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32387, ChEBI:CHEBI:134110;
CC Evidence={ECO:0000269|PubMed:15629124};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z,15Z)-octadecatrienoate + O2 = (13R)-hydroperoxy-
CC (9Z,11E,15Z)-octadecatrienoate; Xref=Rhea:RHEA:51244,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32387, ChEBI:CHEBI:133987;
CC Evidence={ECO:0000269|PubMed:15629124};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15629124, ECO:0000269|PubMed:27313058};
CC Note=Three His residues, the carboxyl oxygen of the C-terminal Ile or
CC Val residue, and a fifth residue, usually Asn, ligate the metal, which
CC binds water to form a catalytic base Mn(2+)OH(2) for hydrogen
CC abstraction. {ECO:0000305|PubMed:27313058};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.1 uM for alpha-linoleate {ECO:0000269|PubMed:15629124};
CC Vmax=18 nmol/min/ug enzyme for alpha-linoleate
CC {ECO:0000269|PubMed:15629124};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12047377,
CC ECO:0000269|PubMed:9582345}.
CC -!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:12047377,
CC ECO:0000269|PubMed:15629124}.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. Manganese lipoxygenase
CC subfamily. {ECO:0000305}.
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DR EMBL; AY040824; AAK81882.2; -; Genomic_DNA.
DR PDB; 5FX8; X-ray; 2.60 A; A/B=1-618.
DR PDBsum; 5FX8; -.
DR AlphaFoldDB; Q8X151; -.
DR SMR; Q8X151; -.
DR SwissLipids; SLP:000001656; -.
DR KEGG; ag:AAK81882; -.
DR SABIO-RK; Q8X151; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0050584; F:linoleate 11-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043651; P:linoleic acid metabolic process; IC:UniProtKB.
DR InterPro; IPR000907; LipOase.
DR InterPro; IPR013819; LipOase_C.
DR InterPro; IPR036226; LipOase_C_sf.
DR PANTHER; PTHR11771; PTHR11771; 1.
DR Pfam; PF00305; Lipoxygenase; 1.
DR SUPFAM; SSF48484; SSF48484; 1.
DR PROSITE; PS51393; LIPOXYGENASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Glycoprotein; Manganese; Metal-binding;
KW Oxidoreductase; Secreted; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000250|UniProtKB:Q8X150"
FT CHAIN 17..618
FT /note="Manganese lipoxygenase"
FT /id="PRO_0000430459"
FT DOMAIN 47..618
FT /note="Lipoxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT REGION 36..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 290
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27313058,
FT ECO:0000305|PubMed:15629124, ECO:0007744|PDB:5FX8"
FT BINDING 294
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27313058,
FT ECO:0000305|PubMed:15629124, ECO:0007744|PDB:5FX8"
FT BINDING 478
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27313058,
FT ECO:0000305|PubMed:15629124, ECO:0007744|PDB:5FX8"
FT BINDING 482
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27313058,
FT ECO:0007744|PDB:5FX8"
FT BINDING 618
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:27313058,
FT ECO:0000305|PubMed:15629124, ECO:0007744|PDB:5FX8"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PDB:5FX8"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PDB:5FX8"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PDB:5FX8"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PDB:5FX8"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PDB:5FX8"
FT CARBOHYD 513
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 290
FT /note="H->Q: Loses manganese cofactor and abolishes
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:15629124"
FT MUTAGEN 294
FT /note="H->E: Loses manganese cofactor and abolishes
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:15629124"
FT MUTAGEN 332
FT /note="G->A: Increases the hydroperoxide isomerase activity
FT severalfold and chnages the regiospecificity of the enzyme,
FT slightly shifting the position of oxygenation from the n-6
FT toward the n-8 and n-10 carbons. May do so by changing the
FT interaction of the hydroperoxides with the catalytic
FT metal."
FT /evidence="ECO:0000269|PubMed:16641090,
FT ECO:0000269|PubMed:18024999, ECO:0000269|PubMed:22822060"
FT MUTAGEN 332
FT /note="G->V,S,T: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:18024999"
FT MUTAGEN 336
FT /note="L->F: Increases the hydroperoxide isomerase
FT activity."
FT /evidence="ECO:0000269|PubMed:22822060"
FT MUTAGEN 336
FT /note="L->V,A,G: Changes the regiospecificity of the enzyme
FT from C-13 toward C-9 with formation of 9S- and 9R-
FT hydroperoxy fatty acids."
FT /evidence="ECO:0000269|PubMed:22822060"
FT MUTAGEN 337
FT /note="F->I: Changes the stereospecificity of the enzyme
FT from 100% 13R- to 69-74% 13S-hydroperoxy fatty acids and
FT increases the oxygenation at C-9, producing mainly the 9S-
FT hydroperoxy stereoisomer from linoleic acid and the 9R-
FT hydroperoxy stereoisomer from alpha-linolenic acid."
FT /evidence="ECO:0000269|PubMed:22822060"
FT MUTAGEN 337
FT /note="F->V,A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:22822060"
FT MUTAGEN 347
FT /note="F->A: Changes the stereospecificity of the enzyme
FT from 13R-HPODE to 13R-, 9S-, and 11-HPODE with almost
FT complete consumption of 11-HPODE to 13R- and 9S-HPOTrE as
FT end products from oxigenation of linoleic acid. Does not
FT affect oxigenation of alpha-linolenic acid."
FT /evidence="ECO:0000269|PubMed:22822060"
FT MUTAGEN 347
FT /note="F->L,V: Changes the stereospecificity of the enzyme
FT from 13R-HPODE to 9S-HPODE as end product from oxigenation
FT of linoleic acid and to 9S- and 13R-HPOTrE from alpha-
FT linolenic acid."
FT /evidence="ECO:0000269|PubMed:22822060"
FT MUTAGEN 478
FT /note="H->E: Loses manganese cofactor and abolishes
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:15629124"
FT MUTAGEN 479
FT /note="H->Q: No effect."
FT /evidence="ECO:0000269|PubMed:15629124"
FT MUTAGEN 482
FT /note="N->Q,L: No effect."
FT /evidence="ECO:0000269|PubMed:15629124,
FT ECO:0000269|PubMed:18024999"
FT MUTAGEN 483
FT /note="Q->N: No effect."
FT /evidence="ECO:0000269|PubMed:15629124"
FT MUTAGEN 485
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:18024999"
FT MUTAGEN 618
FT /note="Missing: Loses manganese cofactor and abolishes
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:15629124"
FT HELIX 56..69
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 77..81
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 86..124
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 131..137
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 152..159
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 161..166
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 192..199
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 203..208
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 218..222
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 235..241
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 242..245
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 246..253
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 268..305
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 313..321
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 328..335
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 342..346
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 351..363
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 374..380
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 384..389
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 396..420
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 428..431
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 434..444
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 460..475
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 477..481
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 485..488
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 489..491
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 493..495
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 498..500
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 506..508
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 520..522
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 526..539
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 542..548
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 551..553
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 558..563
FT /evidence="ECO:0007829|PDB:5FX8"
FT HELIX 566..587
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 600..602
FT /evidence="ECO:0007829|PDB:5FX8"
FT TURN 609..611
FT /evidence="ECO:0007829|PDB:5FX8"
FT STRAND 612..615
FT /evidence="ECO:0007829|PDB:5FX8"
SQ SEQUENCE 618 AA; 67583 MW; 466CFB2801B1D6F2 CRC64;
MRSRILAIVF AARHVAALPL AAEDAAATLS LTSSASSTTV LPSPTQYTLP NNDPNQGARN
ASIARKRELF LYGPSTLGQT TFYPTGELGN NISARDVLLW RQDAANQTAT AYREANETFA
DITSRGGFKT LDDFALLYNG HWKESVPEGI SKGMLSNCTS DLLFSMERLS SNPYVLKRLH
PTKDKLPFSV ESKVVKKLTA TTLEALHKGG RLFLVDHSYQ KKYTPQPGRY AAACQGLFYL
DARSNQFLPL AIKTNVGVDL TYTPLDDKDD WLLAKIMFNN NDLFYSQMYH VLFHTIPEIV
HEAAFRTLSD RHPVMGVLNR LMYQAYAIRP VGGAVLFNPG GFWDQNFGLP ASAAIDFPGS
VYAQGGGGFQ AGYLEKDLRS RGLIGEDSGP RLPHFPFYED AHRLIGAIRR FMQAFVDSTY
GADDGDDGAL LRDYELQNWI AEANGPAQVR DFPAAPLRRR AQLVDVLTHV AWITGGAHHV
MNQGSPVKFS GVLPLHPAAL YAPIPTAKGA TGNGTRAGLL AWLPNERQAV EQVSLLARFN
RAQVGDRKQT VRDAFAAPDL LAGNGPGYAA ANARFVEDTG RISREIAGRG FDGKGLSQGM
PFVWTALNPA VNPFFLSV
