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Protein

L-methionine gamma-lyase

Gene

mdeA

Organism
Pseudomonas putida (Arthrobacter siderocapsulatus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the alpha,gamma-elimination of L-methionine to produce methanethiol, 2-oxobutanoate and ammonia (PubMed:8586629, PubMed:6742420). Is involved in L-methionine catabolism (PubMed:9190812). In fact, shows a multicatalytic function since it also catalyzes gamma-replacement of L-methionine with thiol compounds, alpha,gamma-elimination and gamma-replacement reactions of L-homocysteine and its S-substituted derivatives, O-substituted-L-homoserines and DL-selenomethionine, and, to a lesser extent, alpha,beta-elimination and beta-replacement reactions of L-cysteine, S-methyl-L-cysteine, and O-acetyl-L-serine (PubMed:6742420, PubMed:22785484). Also catalyzes deamination and gamma-addition reactions of L-vinylglycine (PubMed:6742420). Thus, the enzyme is able to cleave C-S, C-Se, and C-O bonds of sulfur, selenium, and oxygen amino acids, respectively (PubMed:6742420, PubMed:22785484).1 Publication3 Publications

Catalytic activityi

L-methionine + H2O = methanethiol + NH3 + 2-oxobutanoate.2 Publications
L-homocysteine + H2O = H2S + NH3 + 2-oxobutanoate.2 Publications

Cofactori

pyridoxal 5'-phosphate3 Publications

Enzyme regulationi

Irreversibly inactivated by DL-propargylglycine.1 Publication

Kineticsi

kcat is 33.4 sec(-1) for the alpha,gamma-elimination of L-methionine. kcat is 71.0 sec(-1) for the alpha,gamma-elimination of DL-homocysteine. kcat is 2.13 sec(-1) for the alpha,beta-elimination of L-cysteine. kcat is 1.58 sec(-1) for the alpha,beta-elimination of S-methyl-L-cysteine. kcat is 2.56 sec(-1) for the alpha,gamma-elimination of O-succinyl-L-homoserine.1 Publication

  1. KM=1.0 mM for L-methionine1 Publication
  2. KM=0.5 mM for L-methionine1 Publication
  3. KM=1.1 mM for DL-homocysteine1 Publication
  4. KM=0.2 mM for L-cysteine1 Publication
  5. KM=0.7 mM for S-methyl-L-cysteine1 Publication
  6. KM=7.2 mM for O-succinyl-L-homoserine1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei114 – 1141SubstrateCombined sources1 Publication
    Binding sitei375 – 3751SubstrateCombined sources1 Publication

    GO - Molecular functioni

    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Ligandi

    Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-284.
    RETL1328306-WGS:GSTH-4259-MONOMER.
    RETL1328306-WGS:GSTH-531-MONOMER.
    RETL1328306-WGS:GSTH-6103-MONOMER.
    BRENDAi4.4.1.11. 5092.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    L-methionine gamma-lyase2 Publications (EC:4.4.1.112 Publications)
    Short name:
    MGL1 Publication
    Alternative name(s):
    Homocysteine desulfhydrase1 Publication (EC:4.4.1.22 Publications)
    L-methioninase
    Gene namesi
    Name:mdeAImported
    OrganismiPseudomonas putida (Arthrobacter siderocapsulatus)
    Taxonomic identifieri303 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaPseudomonadalesPseudomonadaceaePseudomonas

    Pathology & Biotechi

    Biotechnological usei

    The recombinant MGL protein cloned form P.putida has been found to have antitumor efficacy in vitro and in vivo. PEGylated MGL is being developed as a cancer drug.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi61 – 611R → A, E or F: Loss of elimination activity against L-methionine. 1 Publication
    Mutagenesisi116 – 1161C → H: Drastic decrease of the catalytic efficiency of the elimination reaction with L-methionine, by 6700-fold, and increases that with L-cysteine by 7-fold, mainly due to changes in kcat. Loss of ability to catalyze replacement reaction between L-methionine and 2-mercaptoethanol. 1 Publication
    Mutagenesisi116 – 1161C → S: 9% of wild-type elimination activity against L-methionine. 1 Publication
    Mutagenesisi116 – 1161C → T: 40% of wild-type elimination activity against L-methionine. 1 Publication
    Mutagenesisi240 – 2401K → D or E: Marked decrease in elimination activity against both L-methionine and DL-homocysteine. 1 Publication
    Mutagenesisi240 – 2401K → M: 50% reduction in alpha,gamma-elimination activity against DL-homocysteine, while retaining elimination activity against L-methionine and L-cysteine. 1 Publication
    Mutagenesisi241 – 2411D → H or R: 5 to 14-fold reduction in alpha,gamma-elimination activity against L-methionine, while no change in affinity for L-methionine. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 398398L-methionine gamma-lyasePRO_0000114784Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei211 – 2111N6-(pyridoxal phosphate)lysineCombined sources5 Publications

    Expressioni

    Inductioni

    Is under the control of the positive transcriptional regulator MdeR. Forms part of an operon with mdeB.1 Publication

    Interactioni

    Subunit structurei

    Homotetramer; dimer of active dimers.2 Publications

    Structurei

    Secondary structure

    1
    398
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi3 – 75Combined sources
    Helixi10 – 167Combined sources
    Helixi21 – 244Combined sources
    Beta strandi27 – 293Combined sources
    Beta strandi36 – 383Combined sources
    Beta strandi40 – 423Combined sources
    Helixi43 – 508Combined sources
    Beta strandi54 – 563Combined sources
    Turni60 – 623Combined sources
    Helixi65 – 7814Combined sources
    Beta strandi81 – 888Combined sources
    Helixi89 – 10012Combined sources
    Beta strandi106 – 1127Combined sources
    Helixi116 – 1238Combined sources
    Helixi125 – 1284Combined sources
    Beta strandi131 – 1355Combined sources
    Helixi140 – 1467Combined sources
    Beta strandi151 – 1599Combined sources
    Turni161 – 1633Combined sources
    Helixi169 – 1768Combined sources
    Helixi177 – 1793Combined sources
    Beta strandi182 – 1865Combined sources
    Turni188 – 1903Combined sources
    Helixi191 – 1944Combined sources
    Helixi197 – 2004Combined sources
    Beta strandi203 – 2086Combined sources
    Turni209 – 2146Combined sources
    Beta strandi216 – 2183Combined sources
    Beta strandi222 – 2265Combined sources
    Helixi228 – 2369Combined sources
    Helixi238 – 2425Combined sources
    Helixi249 – 25911Combined sources
    Helixi262 – 28120Combined sources
    Beta strandi286 – 2916Combined sources
    Helixi300 – 3067Combined sources
    Beta strandi313 – 3186Combined sources
    Helixi321 – 33111Combined sources
    Beta strandi333 – 3375Combined sources
    Beta strandi343 – 3453Combined sources
    Beta strandi347 – 3493Combined sources
    Helixi351 – 3533Combined sources
    Turni354 – 3563Combined sources
    Beta strandi357 – 3593Combined sources
    Helixi361 – 3666Combined sources
    Beta strandi373 – 3775Combined sources
    Helixi383 – 39715Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1GC0X-ray1.70A/B/C/D1-398[»]
    1GC2X-ray2.00A/B/C/D1-398[»]
    1PG8X-ray2.68A/B/C/D1-398[»]
    1UKJX-ray1.80A/B/C/D1-398[»]
    2O7CX-ray1.70A/B/C/D1-398[»]
    3VK2X-ray2.30A/B/C/D1-398[»]
    3VK3X-ray2.10A/B/C/D1-398[»]
    3VK4X-ray2.61A/B/C/D1-398[»]
    ProteinModelPortaliP13254.
    SMRiP13254. Positions 1-397.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP13254.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni59 – 613Pyridoxal phosphate binding; shared with dimeric partner1 Publication
    Regioni89 – 902Pyridoxal phosphate binding1 Publication
    Regioni208 – 2103Pyridoxal phosphate binding1 Publication

    Sequence similaritiesi

    Family and domain databases

    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProiIPR000277. Cys/Met-Metab_PyrdxlP-dep_enz.
    IPR006237. L-Met_gamma_lys.
    IPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    [Graphical view]
    PANTHERiPTHR11808. PTHR11808. 1 hit.
    PfamiPF01053. Cys_Met_Meta_PP. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001434. CGS. 1 hit.
    SUPFAMiSSF53383. SSF53383. 1 hit.
    TIGRFAMsiTIGR01328. met_gam_lyase. 1 hit.
    PROSITEiPS00868. CYS_MET_METAB_PP. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P13254-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MHGSNKLPGF ATRAIHHGYD PQDHGGALVP PVYQTATFTF PTVEYGAACF
    60 70 80 90 100
    AGEQAGHFYS RISNPTLNLL EARMASLEGG EAGLALASGM GAITSTLWTL
    110 120 130 140 150
    LRPGDEVLLG NTLYGCTFAF LHHGIGEFGV KLRHVDMADL QALEAAMTPA
    160 170 180 190 200
    TRVIYFESPA NPNMHMADIA GVAKIARKHG ATVVVDNTYC TPYLQRPLEL
    210 220 230 240 250
    GADLVVHSAT KYLSGHGDIT AGIVVGSQAL VDRIRLQGLK DMTGAVLSPH
    260 270 280 290 300
    DAALLMRGIK TLNLRMDRHC ANAQVLAEFL ARQPQVELIH YPGLASFPQY
    310 320 330 340 350
    TLARQQMSQP GGMIAFELKG GIGAGRRFMN ALQLFSRAVS LGDAESLAQH
    360 370 380 390
    PASMTHSSYT PEERAHYGIS EGLVRLSVGL EDIDDLLADV QQALKASA
    Length:398
    Mass (Da):42,627
    Last modified:October 1, 1996 - v2
    Checksum:iBD50CD1F34CD71E3
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D88554 Genomic DNA. Translation: BAA13642.1.
    D89015 Genomic DNA. Translation: BAA20553.1.
    PIRiA27691.
    JC4174.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D88554 Genomic DNA. Translation: BAA13642.1.
    D89015 Genomic DNA. Translation: BAA20553.1.
    PIRiA27691.
    JC4174.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1GC0X-ray1.70A/B/C/D1-398[»]
    1GC2X-ray2.00A/B/C/D1-398[»]
    1PG8X-ray2.68A/B/C/D1-398[»]
    1UKJX-ray1.80A/B/C/D1-398[»]
    2O7CX-ray1.70A/B/C/D1-398[»]
    3VK2X-ray2.30A/B/C/D1-398[»]
    3VK3X-ray2.10A/B/C/D1-398[»]
    3VK4X-ray2.61A/B/C/D1-398[»]
    ProteinModelPortaliP13254.
    SMRiP13254. Positions 1-397.
    ModBaseiSearch...
    MobiDBiSearch...

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-284.
    RETL1328306-WGS:GSTH-4259-MONOMER.
    RETL1328306-WGS:GSTH-531-MONOMER.
    RETL1328306-WGS:GSTH-6103-MONOMER.
    BRENDAi4.4.1.11. 5092.

    Miscellaneous databases

    EvolutionaryTraceiP13254.

    Family and domain databases

    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProiIPR000277. Cys/Met-Metab_PyrdxlP-dep_enz.
    IPR006237. L-Met_gamma_lys.
    IPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    [Graphical view]
    PANTHERiPTHR11808. PTHR11808. 1 hit.
    PfamiPF01053. Cys_Met_Meta_PP. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001434. CGS. 1 hit.
    SUPFAMiSSF53383. SSF53383. 1 hit.
    TIGRFAMsiTIGR01328. met_gam_lyase. 1 hit.
    PROSITEiPS00868. CYS_MET_METAB_PP. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    1. "Structural analysis of the L-methionine gamma-lyase gene from Pseudomonas putida."
      Inoue H., Sugimoto M., Inagaki K., Esaki N., Soda K., Tanaka H.
      J. Biochem. 117:1120-1125(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
      Strain: ICR 3460.
    2. "Molecular characterization of the mde operon involved in L-methionine catabolism of Pseudomonas putida."
      Inoue H., Inagaki K., Eriguchi S.I., Tamura T., Esaki N., Soda K., Tanaka H.
      J. Bacteriol. 179:3956-3962(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INDUCTION.
      Strain: ICR 3460.
    3. "Specific labeling of the essential cysteine residue of L-methionine gamma-lyase with a cofactor analogue, N-(bromoacetyl)pyridoxamine phosphate."
      Nakayama T., Esaki N., Tanaka H., Soda K.
      Biochemistry 27:1587-1591(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 91-137 AND 167-213, PYRIDOXAL PHOSPHATE AT LYS-211.
      Strain: ICR 3460.
    4. Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
      Strain: ICR 3460.
    5. "Development of recombinant methioninase to target the general cancer-specific metabolic defect of methionine dependence: a 40-year odyssey."
      Hoffman R.M.
      Expert Opin. Biol. Ther. 15:21-31(2015) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW, BIOTECHNOLOGY.
    6. "Crystal structure of the pyridoxal 5'-phosphate dependent L-methionine gamma-lyase from Pseudomonas putida."
      Motoshima H., Inagaki K., Kumasaka T., Furuichi M., Inoue H., Tamura T., Esaki N., Soda K., Tanaka N., Yamamoto M., Tanaka H.
      J. Biochem. 128:349-354(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS).
    7. "Crystal structure of L-methionine alpha-, gamma-lyase."
      Allen T.W., Sridhar V., Prasad G.S., Han Q., Xu M., Tan Y., Hoffman R.M., Ramaswamy S.
      Submitted (MAY-2003) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) IN COVALENT COMPLEX WITH PLP.
    8. "Detailed structure of L-methionine-lyase from Pseudomonas putida."
      Misaki S., Takimoto A., Takakura T., Yoshioka T., Yamashita M., Tamura T., Tanaka H., Inagaki K.
      Submitted (AUG-2003) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COVALENT COMPLEX WITH PLP.
    9. "Structure of the antitumour enzyme L-methionine gamma-lyase from Pseudomonas putida at 1.8 A resolution."
      Kudou D., Misaki S., Yamashita M., Tamura T., Takakura T., Yoshioka T., Yagi S., Hoffman R.M., Takimoto A., Esaki N., Inagaki K.
      J. Biochem. 141:535-544(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COVALENT COMPLEX WITH PLP, COFACTOR, SUBUNIT, MUTAGENESIS OF ARG-61 AND CYS-116.
      Strain: ICR 3460.
    10. "The role of amino acid residues in the active site of L-methionine gamma-lyase from Pseudomonas putida."
      Fukumoto M., Kudou D., Murano S., Shiba T., Sato D., Tamura T., Harada S., Inagaki K.
      Biosci. Biotechnol. Biochem. 76:1275-1284(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANT HIS-116 IN COMPLEXES WITH L-HOMOCYSTEINE; METHIONINE AND PLP, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, ENZYME REGULATION, MUTAGENESIS OF CYS-116; LYS-240 AND ASP-241.

    Entry informationi

    Entry nameiMEGL_PSEPU
    AccessioniPrimary (citable) accession number: P13254
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1990
    Last sequence update: October 1, 1996
    Last modified: June 8, 2016
    This is version 95 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Direct protein sequencing

    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.