LMO_MYCSM
ID LMO_MYCSM Reviewed; 394 AA.
AC P21795;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=L-lactate 2-monooxygenase {ECO:0000303|PubMed:2324094};
DE Short=LMO {ECO:0000303|PubMed:30207005};
DE EC=1.13.12.4 {ECO:0000269|PubMed:4640938};
DE AltName: Full=Lactate monooxygenase {ECO:0000303|PubMed:30207005};
OS Mycolicibacterium smegmatis (Mycobacterium smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=1772;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 14468 / DSM 43277 / NCIB 9953 / NCTC 10265 / W-113;
RX PubMed=2324094; DOI=10.1016/s0021-9258(19)39195-1;
RA Giegel D.A., Williams C.H. Jr., Massey V.;
RT "L-lactate 2-monooxygenase from Mycobacterium smegmatis. Cloning,
RT nucleotide sequence, and primary structure homology within an enzyme
RT family.";
RL J. Biol. Chem. 265:6626-6632(1990).
RN [2]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=3571231; DOI=10.1016/s0021-9258(18)45632-3;
RA Giegel D.A., Massey V., Williams C.H. Jr.;
RT "L-lactate-2-monooxygenase. Sequence of peptides containing residues
RT modified by 1-fluoro-2,4-dinitrobenzene.";
RL J. Biol. Chem. 262:5705-5710(1987).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=4640938; DOI=10.1016/s0021-9258(20)81814-6;
RA Lockridge O., Massey V., Sullivan P.A.;
RT "Mechanism of action of the flavoenzyme lactate oxidase.";
RL J. Biol. Chem. 247:8097-8106(1972).
RN [4] {ECO:0007744|PDB:6DVH, ECO:0007744|PDB:6DVI}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF WILD-TYPE AND MUTANT ALA-204 IN
RP COMPLEX WITH FMN, COFACTOR, AND SUBUNIT.
RX PubMed=30207005; DOI=10.1002/pro.3506;
RA Kean K.M., Karplus P.A.;
RT "Structure and role for active site lid of lactate monooxygenase from
RT Mycobacterium smegmatis.";
RL Protein Sci. 28:135-149(2019).
CC -!- FUNCTION: Catalyzes the oxidative decarboxylation of (S)-lactate (L-
CC lactate) to acetate and carbon dioxide. Its physiological role remains
CC unknown. {ECO:0000269|PubMed:4640938}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate + O2 = acetate + CO2 + H2O; Xref=Rhea:RHEA:16513,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16651, ChEBI:CHEBI:30089; EC=1.13.12.4;
CC Evidence={ECO:0000269|PubMed:4640938};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:30207005};
CC Note=Binds 1 FMN per subunit. {ECO:0000269|PubMed:30207005};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=kcat is 6250 min(-1). {ECO:0000269|PubMed:4640938};
CC -!- SUBUNIT: Homotetramer. {ECO:0000305|PubMed:30207005}.
CC -!- MISCELLANEOUS: This enzyme proceeds along a 'coupled pathway', wherein
CC rather than releasing the alpha-keto-acid as a product (in this case
CC pyruvate), it remains in the active site, and after reaction with
CC hydrogen peroxide undergoes an oxidative decarboxylation to produce
CC acetate, carbon dioxide, and water. {ECO:0000305|PubMed:30207005}.
CC -!- SIMILARITY: Belongs to the FMN-dependent alpha-hydroxy acid
CC dehydrogenase family. {ECO:0000305}.
CC -!- CAUTION: This enzyme was originally referred to as 'lactate oxidase'
CC but this acetate producing enzyme is now referred to as 'lactate
CC monooxygenase' (LMO), and 'lactate oxidase' (LOX) refers to a related
CC flavoenzyme that converts lactate and molecular oxygen to pyruvate and
CC hydrogen peroxide. {ECO:0000305|PubMed:30207005}.
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DR EMBL; J05402; AAA60429.1; -; Genomic_DNA.
DR PIR; A35745; A35745.
DR RefSeq; WP_003895417.1; NZ_UGQO01000002.1.
DR PDB; 6DVH; X-ray; 1.70 A; A/B/C/D/E/F=1-394.
DR PDB; 6DVI; X-ray; 2.30 A; A/B/C/D/E/F=1-394.
DR PDBsum; 6DVH; -.
DR PDBsum; 6DVI; -.
DR AlphaFoldDB; P21795; -.
DR SMR; P21795; -.
DR GeneID; 66735327; -.
DR OMA; FQYEIYL; -.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0050040; F:lactate 2-monooxygenase activity; IEA:UniProtKB-EC.
DR CDD; cd03332; LMO_FMN; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR012133; Alpha-hydoxy_acid_DH_FMN.
DR InterPro; IPR000262; FMN-dep_DH.
DR InterPro; IPR037396; FMN_HAD.
DR InterPro; IPR008259; FMN_hydac_DH_AS.
DR InterPro; IPR037350; LMO_FMN.
DR Pfam; PF01070; FMN_dh; 1.
DR PIRSF; PIRSF000138; Al-hdrx_acd_dh; 1.
DR PROSITE; PS00557; FMN_HYDROXY_ACID_DH_1; 1.
DR PROSITE; PS51349; FMN_HYDROXY_ACID_DH_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Flavoprotein; FMN; Monooxygenase;
KW Oxidoreductase.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..394
FT /note="L-lactate 2-monooxygenase"
FT /id="PRO_0000206326"
FT DOMAIN 19..394
FT /note="FMN hydroxy acid dehydrogenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT ACT_SITE 291
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 45
FT /ligand="a 2-oxocarboxylate"
FT /ligand_id="ChEBI:CHEBI:35179"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 98..100
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:30207005,
FT ECO:0007744|PDB:6DVI"
FT BINDING 129
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:30207005,
FT ECO:0007744|PDB:6DVI"
FT BINDING 151
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:30207005,
FT ECO:0007744|PDB:6DVI"
FT BINDING 153
FT /ligand="a 2-oxocarboxylate"
FT /ligand_id="ChEBI:CHEBI:35179"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 179
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:30207005,
FT ECO:0007744|PDB:6DVI"
FT BINDING 188
FT /ligand="a 2-oxocarboxylate"
FT /ligand_id="ChEBI:CHEBI:35179"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 267
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:30207005,
FT ECO:0007744|PDB:6DVI"
FT BINDING 294
FT /ligand="a 2-oxocarboxylate"
FT /ligand_id="ChEBI:CHEBI:35179"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00683"
FT BINDING 321..325
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:30207005,
FT ECO:0007744|PDB:6DVI"
FT BINDING 345
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:30207005,
FT ECO:0007744|PDB:6DVI"
FT HELIX 4..6
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 7..15
FT /evidence="ECO:0007829|PDB:6DVH"
FT TURN 16..18
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 27..37
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 40..47
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 54..61
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 88..96
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 102..105
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 136..142
FT /evidence="ECO:0007829|PDB:6DVH"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 148..152
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 158..171
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 189..193
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 212..222
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 226..231
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 233..236
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 237..243
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 250..258
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 264..269
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 272..280
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 302..313
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 327..335
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 339..343
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 345..377
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:6DVH"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:6DVH"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:6DVH"
SQ SEQUENCE 394 AA; 42747 MW; D535A910E7F7232A CRC64;
MSNWGDYENE IYGQGLVGVA PTLPMSYADW EAHAQQALPP GVLSYVAGGS GDEHTQRANV
EAFKHWGLMP RMLMAATERD LSVELWGKTW AAPMFFAPIG VIALCAQDGH GDAASAQASA
RTGVPYITST LAVSSLEDIR KHAGDTPAYF QLYYPEDRDL AESFIRRAEE AGYDGLVITL
DTWIFGWRPR DLTISNFPFL RGLCLTNYVT DPVFQKKFKA HSGVEAEGLR DNPRLAADFW
HGLFGHSVTW EDIDWVRSIT KMPVILKGIQ HPDDARRAVD SGVDGIYCSN HGGRQANGGL
PALDCLPEVV KASGDTPVLF DSGIRTGADV VKALAMGASA VGIGRPYAWG AALGGSKGIE
HVARSLLAEA DLIMAVDGYR NLKELTIDAL RPTR
