Entry sw:MEGL_PSEPU

ID   MEGL_PSEPU              Reviewed;         398 AA.
AC   P13254;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   02-NOV-2016, entry version 98.
DE   RecName: Full=L-methionine gamma-lyase {ECO:0000303|PubMed:6742420, ECO:0000303|PubMed:8586629};
DE            Short=MGL {ECO:0000303|PubMed:10965031};
DE            EC=4.4.1.11 {ECO:0000269|PubMed:22785484, ECO:0000269|PubMed:6742420};
DE   AltName: Full=Homocysteine desulfhydrase {ECO:0000305|PubMed:6742420};
DE            EC=4.4.1.2 {ECO:0000269|PubMed:22785484, ECO:0000269|PubMed:6742420};
DE   AltName: Full=L-methioninase;
GN   Name=mdeA {ECO:0000312|EMBL:BAA20553.1};
OS   Pseudomonas putida (Arthrobacter siderocapsulatus).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC   Pseudomonadaceae; Pseudomonas.
OX   NCBI_TaxID=303;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC   STRAIN=ICR 3460;
RX   PubMed=8586629;
RA   Inoue H., Sugimoto M., Inagaki K., Esaki N., Soda K., Tanaka H.;
RT   "Structural analysis of the L-methionine gamma-lyase gene from
RT   Pseudomonas putida.";
RL   J. Biochem. 117:1120-1125(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION.
RC   STRAIN=ICR 3460;
RX   PubMed=9190812;
RA   Inoue H., Inagaki K., Eriguchi S.I., Tamura T., Esaki N., Soda K.,
RA   Tanaka H.;
RT   "Molecular characterization of the mde operon involved in L-methionine
RT   catabolism of Pseudomonas putida.";
RL   J. Bacteriol. 179:3956-3962(1997).
RN   [3]
RP   PROTEIN SEQUENCE OF 91-137 AND 167-213, AND PYRIDOXAL PHOSPHATE AT
RP   LYS-211.
RC   STRAIN=ICR 3460;
RX   PubMed=3365412; DOI=10.1021/bi00405a029;
RA   Nakayama T., Esaki N., Tanaka H., Soda K.;
RT   "Specific labeling of the essential cysteine residue of L-methionine
RT   gamma-lyase with a cofactor analogue, N-(bromoacetyl)pyridoxamine
RT   phosphate.";
RL   Biochemistry 27:1587-1591(1988).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC   STRAIN=ICR 3460;
RX   PubMed=6742420; DOI=10.1016/0003-2697(84)90832-7;
RA   Nakayama T., Esaki N., Sugie K., Beresov T.T., Tanaka H., Soda K.;
RT   "Purification of bacterial L-methionine gamma-lyase.";
RL   Anal. Biochem. 138:421-424(1984).
RN   [5]
RP   REVIEW, AND BIOTECHNOLOGY.
RX   PubMed=25439528; DOI=10.1517/14712598.2015.963050;
RA   Hoffman R.M.;
RT   "Development of recombinant methioninase to target the general cancer-
RT   specific metabolic defect of methionine dependence: a 40-year
RT   odyssey.";
RL   Expert Opin. Biol. Ther. 15:21-31(2015).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS).
RX   PubMed=10965031; DOI=10.1093/oxfordjournals.jbchem.a022760;
RA   Motoshima H., Inagaki K., Kumasaka T., Furuichi M., Inoue H.,
RA   Tamura T., Esaki N., Soda K., Tanaka N., Yamamoto M., Tanaka H.;
RT   "Crystal structure of the pyridoxal 5'-phosphate dependent L-
RT   methionine gamma-lyase from Pseudomonas putida.";
RL   J. Biochem. 128:349-354(2000).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) IN COVALENT COMPLEX WITH PLP.
RA   Allen T.W., Sridhar V., Prasad G.S., Han Q., Xu M., Tan Y.,
RA   Hoffman R.M., Ramaswamy S.;
RT   "Crystal structure of L-methionine alpha-, gamma-lyase.";
RL   Submitted (MAY-2003) to the PDB data bank.
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COVALENT COMPLEX WITH PLP.
RA   Misaki S., Takimoto A., Takakura T., Yoshioka T., Yamashita M.,
RA   Tamura T., Tanaka H., Inagaki K.;
RT   "Detailed structure of L-methionine-lyase from Pseudomonas putida.";
RL   Submitted (AUG-2003) to the PDB data bank.
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COVALENT COMPLEX WITH PLP,
RP   COFACTOR, SUBUNIT, AND MUTAGENESIS OF ARG-61 AND CYS-116.
RC   STRAIN=ICR 3460;
RX   PubMed=17289792; DOI=10.1093/jb/mvm055;
RA   Kudou D., Misaki S., Yamashita M., Tamura T., Takakura T.,
RA   Yoshioka T., Yagi S., Hoffman R.M., Takimoto A., Esaki N., Inagaki K.;
RT   "Structure of the antitumour enzyme L-methionine gamma-lyase from
RT   Pseudomonas putida at 1.8 A resolution.";
RL   J. Biochem. 141:535-544(2007).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANT HIS-116 IN COMPLEXES
RP   WITH L-HOMOCYSTEINE; METHIONINE AND PLP, FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, ENZYME REGULATION, AND
RP   MUTAGENESIS OF CYS-116; LYS-240 AND ASP-241.
RX   PubMed=22785484; DOI=10.1271/bbb.110906;
RA   Fukumoto M., Kudou D., Murano S., Shiba T., Sato D., Tamura T.,
RA   Harada S., Inagaki K.;
RT   "The role of amino acid residues in the active site of L-methionine
RT   gamma-lyase from Pseudomonas putida.";
RL   Biosci. Biotechnol. Biochem. 76:1275-1284(2012).
CC   -!- FUNCTION: Catalyzes the alpha,gamma-elimination of L-methionine to
CC       produce methanethiol, 2-oxobutanoate and ammonia (PubMed:8586629,
CC       PubMed:6742420). Is involved in L-methionine catabolism
CC       (PubMed:9190812). In fact, shows a multicatalytic function since
CC       it also catalyzes gamma-replacement of L-methionine with thiol
CC       compounds, alpha,gamma-elimination and gamma-replacement reactions
CC       of L-homocysteine and its S-substituted derivatives, O-
CC       substituted-L-homoserines and DL-selenomethionine, and, to a
CC       lesser extent, alpha,beta-elimination and beta-replacement
CC       reactions of L-cysteine, S-methyl-L-cysteine, and O-acetyl-L-
CC       serine (PubMed:6742420, PubMed:22785484). Also catalyzes
CC       deamination and gamma-addition reactions of L-vinylglycine
CC       (PubMed:6742420). Thus, the enzyme is able to cleave C-S, C-Se,
CC       and C-O bonds of sulfur, selenium, and oxygen amino acids,
CC       respectively (PubMed:6742420, PubMed:22785484).
CC       {ECO:0000269|PubMed:22785484, ECO:0000269|PubMed:6742420,
CC       ECO:0000269|PubMed:8586629, ECO:0000305|PubMed:9190812}.
CC   -!- CATALYTIC ACTIVITY: L-methionine + H(2)O = methanethiol + NH(3) +
CC       2-oxobutanoate. {ECO:0000269|PubMed:22785484,
CC       ECO:0000269|PubMed:6742420}.
CC   -!- CATALYTIC ACTIVITY: L-homocysteine + H(2)O = H(2)S + NH(3) + 2-
CC       oxobutanoate. {ECO:0000269|PubMed:22785484,
CC       ECO:0000269|PubMed:6742420}.
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000269|PubMed:17289792,
CC         ECO:0000269|PubMed:22785484, ECO:0000269|PubMed:6742420};
CC   -!- ENZYME REGULATION: Irreversibly inactivated by DL-
CC       propargylglycine. {ECO:0000269|PubMed:22785484}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.0 mM for L-methionine {ECO:0000269|PubMed:6742420};
CC         KM=0.5 mM for L-methionine {ECO:0000269|PubMed:22785484};
CC         KM=1.1 mM for DL-homocysteine {ECO:0000269|PubMed:22785484};
CC         KM=0.2 mM for L-cysteine {ECO:0000269|PubMed:22785484};
CC         KM=0.7 mM for S-methyl-L-cysteine {ECO:0000269|PubMed:22785484};
CC         KM=7.2 mM for O-succinyl-L-homoserine
CC         {ECO:0000269|PubMed:22785484};
CC         Note=kcat is 33.4 sec(-1) for the alpha,gamma-elimination of L-
CC         methionine. kcat is 71.0 sec(-1) for the alpha,gamma-elimination
CC         of DL-homocysteine. kcat is 2.13 sec(-1) for the alpha,beta-
CC         elimination of L-cysteine. kcat is 1.58 sec(-1) for the
CC         alpha,beta-elimination of S-methyl-L-cysteine. kcat is 2.56
CC         sec(-1) for the alpha,gamma-elimination of O-succinyl-L-
CC         homoserine. {ECO:0000269|PubMed:22785484};
CC   -!- SUBUNIT: Homotetramer; dimer of active dimers.
CC       {ECO:0000269|PubMed:17289792, ECO:0000269|PubMed:6742420}.
CC   -!- INDUCTION: Is under the control of the positive transcriptional
CC       regulator MdeR. Forms part of an operon with mdeB.
CC       {ECO:0000269|PubMed:9190812}.
CC   -!- BIOTECHNOLOGY: The recombinant MGL protein cloned form P.putida
CC       has been found to have antitumor efficacy in vitro and in vivo.
CC       PEGylated MGL is being developed as a cancer drug.
CC       {ECO:0000303|PubMed:25439528}.
CC   -!- SIMILARITY: Belongs to the trans-sulfuration enzymes family. L-
CC       methionine gamma-lyase subfamily. {ECO:0000305}.
DR   EMBL; D88554; BAA13642.1; -; Genomic_DNA.
DR   EMBL; D89015; BAA20553.1; -; Genomic_DNA.
DR   PIR; A27691; A27691.
DR   PIR; JC4174; JC4174.
DR   PDB; 1GC0; X-ray; 1.70 A; A/B/C/D=1-398.
DR   PDB; 1GC2; X-ray; 2.00 A; A/B/C/D=1-398.
DR   PDB; 1PG8; X-ray; 2.68 A; A/B/C/D=1-398.
DR   PDB; 1UKJ; X-ray; 1.80 A; A/B/C/D=1-398.
DR   PDB; 2O7C; X-ray; 1.70 A; A/B/C/D=1-398.
DR   PDB; 3VK2; X-ray; 2.30 A; A/B/C/D=1-398.
DR   PDB; 3VK3; X-ray; 2.10 A; A/B/C/D=1-398.
DR   PDB; 3VK4; X-ray; 2.61 A; A/B/C/D=1-398.
DR   PDBsum; 1GC0; -.
DR   PDBsum; 1GC2; -.
DR   PDBsum; 1PG8; -.
DR   PDBsum; 1UKJ; -.
DR   PDBsum; 2O7C; -.
DR   PDBsum; 3VK2; -.
DR   PDBsum; 3VK3; -.
DR   PDBsum; 3VK4; -.
DR   ProteinModelPortal; P13254; -.
DR   SMR; P13254; -.
DR   BioCyc; MetaCyc:MONOMER-284; -.
DR   BRENDA; 4.4.1.11; 5092.
DR   EvolutionaryTrace; P13254; -.
DR   GO; GO:0047982; F:homocysteine desulfhydrase activity; IEA:UniProtKB-EC.
DR   GO; GO:0018826; F:methionine gamma-lyase activity; IEA:UniProtKB-EC.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   CDD; cd00614; CGS_like; 1.
DR   Gene3D; 3.40.640.10; -; 1.
DR   Gene3D; 3.90.1150.10; -; 1.
DR   InterPro; IPR000277; Cys/Met-Metab_PyrdxlP-dep_enz.
DR   InterPro; IPR006237; L-Met_gamma_lys.
DR   InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR   InterPro; IPR015421; PyrdxlP-dep_Trfase_major_sub1.
DR   InterPro; IPR015422; PyrdxlP-dep_Trfase_major_sub2.
DR   PANTHER; PTHR11808; PTHR11808; 1.
DR   Pfam; PF01053; Cys_Met_Meta_PP; 1.
DR   PIRSF; PIRSF001434; CGS; 1.
DR   SUPFAM; SSF53383; SSF53383; 1.
DR   TIGRFAMs; TIGR01328; met_gam_lyase; 1.
DR   PROSITE; PS00868; CYS_MET_METAB_PP; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Lyase; Pyridoxal phosphate.
FT   CHAIN         1    398       L-methionine gamma-lyase.
FT                                /FTId=PRO_0000114784.
FT   REGION       59     61       Pyridoxal phosphate binding; shared with
FT                                dimeric partner. {ECO:0000269|Ref.7}.
FT   REGION       89     90       Pyridoxal phosphate binding.
FT                                {ECO:0000269|Ref.7}.
FT   REGION      208    210       Pyridoxal phosphate binding.
FT                                {ECO:0000269|Ref.7}.
FT   BINDING     114    114       Substrate. {ECO:0000244|PDB:3VK3,
FT                                ECO:0000244|PDB:3VK4,
FT                                ECO:0000269|PubMed:22785484}.
FT   BINDING     375    375       Substrate. {ECO:0000244|PDB:3VK3,
FT                                ECO:0000244|PDB:3VK4,
FT                                ECO:0000269|PubMed:22785484}.
FT   MOD_RES     211    211       N6-(pyridoxal phosphate)lysine.
FT                                {ECO:0000244|PDB:1UKJ,
FT                                ECO:0000269|PubMed:17289792,
FT                                ECO:0000269|PubMed:22785484,
FT                                ECO:0000269|PubMed:3365412,
FT                                ECO:0000269|Ref.7, ECO:0000269|Ref.8}.
FT   MUTAGEN      61     61       R->A,E,F: Loss of elimination activity
FT                                against L-methionine.
FT                                {ECO:0000269|PubMed:17289792}.
FT   MUTAGEN     116    116       C->H: Drastic decrease of the catalytic
FT                                efficiency of the elimination reaction
FT                                with L-methionine, by 6700-fold, and
FT                                increases that with L-cysteine by 7-fold,
FT                                mainly due to changes in kcat. Loss of
FT                                ability to catalyze replacement reaction
FT                                between L-methionine and 2-
FT                                mercaptoethanol.
FT                                {ECO:0000269|PubMed:22785484}.
FT   MUTAGEN     116    116       C->S: 9% of wild-type elimination
FT                                activity against L-methionine.
FT                                {ECO:0000269|PubMed:17289792}.
FT   MUTAGEN     116    116       C->T: 40% of wild-type elimination
FT                                activity against L-methionine.
FT                                {ECO:0000269|PubMed:17289792}.
FT   MUTAGEN     240    240       K->D,E: Marked decrease in elimination
FT                                activity against both L-methionine and
FT                                DL-homocysteine.
FT                                {ECO:0000269|PubMed:22785484}.
FT   MUTAGEN     240    240       K->M: 50% reduction in alpha,gamma-
FT                                elimination activity against DL-
FT                                homocysteine, while retaining elimination
FT                                activity against L-methionine and L-
FT                                cysteine. {ECO:0000269|PubMed:22785484}.
FT   MUTAGEN     241    241       D->H,R: 5 to 14-fold reduction in
FT                                alpha,gamma-elimination activity against
FT                                L-methionine, while no change in affinity
FT                                for L-methionine.
FT                                {ECO:0000269|PubMed:22785484}.
FT   STRAND        3      7       {ECO:0000244|PDB:2O7C}.
FT   HELIX        10     16       {ECO:0000244|PDB:1GC0}.
FT   HELIX        21     24       {ECO:0000244|PDB:1GC0}.
FT   STRAND       27     29       {ECO:0000244|PDB:1GC0}.
FT   STRAND       36     38       {ECO:0000244|PDB:2O7C}.
FT   STRAND       40     42       {ECO:0000244|PDB:3VK3}.
FT   HELIX        43     50       {ECO:0000244|PDB:2O7C}.
FT   STRAND       54     56       {ECO:0000244|PDB:3VK4}.
FT   TURN         60     62       {ECO:0000244|PDB:2O7C}.
FT   HELIX        65     78       {ECO:0000244|PDB:1GC0}.
FT   STRAND       81     88       {ECO:0000244|PDB:1GC0}.
FT   HELIX        89    100       {ECO:0000244|PDB:1GC0}.
FT   STRAND      106    112       {ECO:0000244|PDB:1GC0}.
FT   HELIX       116    123       {ECO:0000244|PDB:1GC0}.
FT   HELIX       125    128       {ECO:0000244|PDB:1GC0}.
FT   STRAND      131    135       {ECO:0000244|PDB:1GC0}.
FT   HELIX       140    146       {ECO:0000244|PDB:1GC0}.
FT   STRAND      151    159       {ECO:0000244|PDB:1GC0}.
FT   TURN        161    163       {ECO:0000244|PDB:1GC0}.
FT   HELIX       169    176       {ECO:0000244|PDB:1GC0}.
FT   HELIX       177    179       {ECO:0000244|PDB:1GC0}.
FT   STRAND      182    186       {ECO:0000244|PDB:1GC0}.
FT   TURN        188    190       {ECO:0000244|PDB:1GC0}.
FT   HELIX       191    194       {ECO:0000244|PDB:1GC0}.
FT   HELIX       197    200       {ECO:0000244|PDB:1GC0}.
FT   STRAND      203    208       {ECO:0000244|PDB:1GC0}.
FT   TURN        209    214       {ECO:0000244|PDB:1GC0}.
FT   STRAND      216    218       {ECO:0000244|PDB:1GC0}.
FT   STRAND      222    226       {ECO:0000244|PDB:1GC0}.
FT   HELIX       228    236       {ECO:0000244|PDB:1GC0}.
FT   HELIX       238    242       {ECO:0000244|PDB:1GC0}.
FT   HELIX       249    259       {ECO:0000244|PDB:1GC0}.
FT   HELIX       262    281       {ECO:0000244|PDB:1GC0}.
FT   STRAND      286    291       {ECO:0000244|PDB:1GC0}.
FT   HELIX       300    306       {ECO:0000244|PDB:2O7C}.
FT   STRAND      313    318       {ECO:0000244|PDB:1GC0}.
FT   HELIX       321    331       {ECO:0000244|PDB:1GC0}.
FT   STRAND      333    337       {ECO:0000244|PDB:1GC0}.
FT   STRAND      343    345       {ECO:0000244|PDB:2O7C}.
FT   STRAND      347    349       {ECO:0000244|PDB:1GC0}.
FT   HELIX       351    353       {ECO:0000244|PDB:1GC0}.
FT   TURN        354    356       {ECO:0000244|PDB:1GC0}.
FT   STRAND      357    359       {ECO:0000244|PDB:1GC0}.
FT   HELIX       361    366       {ECO:0000244|PDB:1GC0}.
FT   STRAND      373    377       {ECO:0000244|PDB:1GC0}.
FT   HELIX       383    397       {ECO:0000244|PDB:1GC0}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT        12    395       ipfam:Cys_Met_Meta_PP [T]
FT   MYHIT       203    217       ipat:CYS_MET_METAB_PP [T]
SQ   SEQUENCE   398 AA;  42627 MW;  BD50CD1F34CD71E3 CRC64;
     MHGSNKLPGF ATRAIHHGYD PQDHGGALVP PVYQTATFTF PTVEYGAACF AGEQAGHFYS
     RISNPTLNLL EARMASLEGG EAGLALASGM GAITSTLWTL LRPGDEVLLG NTLYGCTFAF
     LHHGIGEFGV KLRHVDMADL QALEAAMTPA TRVIYFESPA NPNMHMADIA GVAKIARKHG
     ATVVVDNTYC TPYLQRPLEL GADLVVHSAT KYLSGHGDIT AGIVVGSQAL VDRIRLQGLK
     DMTGAVLSPH DAALLMRGIK TLNLRMDRHC ANAQVLAEFL ARQPQVELIH YPGLASFPQY
     TLARQQMSQP GGMIAFELKG GIGAGRRFMN ALQLFSRAVS LGDAESLAQH PASMTHSSYT
     PEERAHYGIS EGLVRLSVGL EDIDDLLADV QQALKASA
//