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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

Manual assertion based on experiment ini

  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)DescriptionActionsGraphical viewLength
    Binding sitei114SubstrateCombined sources1 Publication1
    Binding sitei375SubstrateCombined sources1 Publication1

    GO - Molecular functioni

    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Ligandi

    Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-284.
    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)DescriptionActionsGraphical viewLength
    Mutagenesisi61R → A, E or F: Loss of elimination activity against L-methionine. 1 Publication1
    Mutagenesisi116C → 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 Publication1
    Mutagenesisi116C → S: 9% of wild-type elimination activity against L-methionine. 1 Publication1
    Mutagenesisi116C → T: 40% of wild-type elimination activity against L-methionine. 1 Publication1
    Mutagenesisi240K → D or E: Marked decrease in elimination activity against both L-methionine and DL-homocysteine. 1 Publication1
    Mutagenesisi240K → M: 50% reduction in alpha,gamma-elimination activity against DL-homocysteine, while retaining elimination activity against L-methionine and L-cysteine. 1 Publication1
    Mutagenesisi241D → 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 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001147841 – 398L-methionine gamma-lyaseAdd BLAST398

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei211N6-(pyridoxal phosphate)lysineCombined sources5 Publications1

    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

    1398
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi3 – 7Combined sources5
    Helixi10 – 16Combined sources7
    Helixi21 – 24Combined sources4
    Beta strandi27 – 29Combined sources3
    Beta strandi36 – 38Combined sources3
    Beta strandi40 – 42Combined sources3
    Helixi43 – 50Combined sources8
    Beta strandi54 – 56Combined sources3
    Turni60 – 62Combined sources3
    Helixi65 – 78Combined sources14
    Beta strandi81 – 88Combined sources8
    Helixi89 – 100Combined sources12
    Beta strandi106 – 112Combined sources7
    Helixi116 – 123Combined sources8
    Helixi125 – 128Combined sources4
    Beta strandi131 – 135Combined sources5
    Helixi140 – 146Combined sources7
    Beta strandi151 – 159Combined sources9
    Turni161 – 163Combined sources3
    Helixi169 – 176Combined sources8
    Helixi177 – 179Combined sources3
    Beta strandi182 – 186Combined sources5
    Turni188 – 190Combined sources3
    Helixi191 – 194Combined sources4
    Helixi197 – 200Combined sources4
    Beta strandi203 – 208Combined sources6
    Turni209 – 214Combined sources6
    Beta strandi216 – 218Combined sources3
    Beta strandi222 – 226Combined sources5
    Helixi228 – 236Combined sources9
    Helixi238 – 242Combined sources5
    Helixi249 – 259Combined sources11
    Helixi262 – 281Combined sources20
    Beta strandi286 – 291Combined sources6
    Helixi300 – 306Combined sources7
    Beta strandi313 – 318Combined sources6
    Helixi321 – 331Combined sources11
    Beta strandi333 – 337Combined sources5
    Beta strandi343 – 345Combined sources3
    Beta strandi347 – 349Combined sources3
    Helixi351 – 353Combined sources3
    Turni354 – 356Combined sources3
    Beta strandi357 – 359Combined sources3
    Helixi361 – 366Combined sources6
    Beta strandi373 – 377Combined sources5
    Helixi383 – 397Combined sources15

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP13254.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni59 – 61Pyridoxal phosphate binding; shared with dimeric partner1 Publication3
    Regioni89 – 90Pyridoxal phosphate binding1 Publication2
    Regioni208 – 210Pyridoxal phosphate binding1 Publication3

    Sequence similaritiesi

    Family and domain databases

    CDDicd00614. CGS_like. 1 hit.
    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
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-284.
    BRENDAi4.4.1.11. 5092.

    Miscellaneous databases

    EvolutionaryTraceiP13254.

    Family and domain databases

    CDDicd00614. CGS_like. 1 hit.
    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...

    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: November 2, 2016
    This is version 98 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.