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3e5d

    Table of contents
    1. 1. Protein Summary
    2. 2. Ligand Summary

    Title Crystal structure of Putative Glyoxalase I (YP_013033.1) from LISTERIA MONOCYTOGENES 4b F2365 at 2.70 A resolution. To be published
    Site JCSG
    PDB Id 3e5d Target Id 367570
    Molecular Characteristics
    Source Listeria monocytogenes str. 4b f2365
    Alias Ids TPS6323,YP_013033.1, 86391 Molecular Weight 14243.18 Da.
    Residues 126 Isoelectric Point 4.69
    Sequence mkiehvalwttnleqmkqfyvtyfgatandlyenktkgfnsyflsfedgarleimsrtdvtgkttgenl gwahiaistgtkeavdelteklrqdgfaiageprmtgdgyyesvvldpegnrieitw
      BLAST   FFAS

    Structure Determination
    Method XRAY Chains 1
    Resolution (Å) 2.70 Rfree 0.198
    Matthews' coefficent 5.42 Rfactor 0.172
    Waters 2 Solvent Content 77.32

    Ligand Information
    Ligands
    Metals

    Jmol

     
    Google Scholar output for 3e5d
    1. Structural Variation in Bacterial Glyoxalase I Enzymes
    U Suttisansanee, K Lau, S Lagishetty, KN Rao - Journal of Biological , 2011 - ASBMB
     

    Protein Summary

    This protein YP_013033.1 is annotated as a glyoxalase family (Pfam PF00903, Glyoxalase/Bleomycin resistant protein/Dioxygenase superfamily, E-value: 9.1e-21) protein from Listeria monocytogenes str. 4b F2365.

    There are 2 kinds of known glyoxalases, glyoxalase I and glyoxalase II (not structurally related) and they play important roles in cellular detoxification (Ref1, Ref2) in two steps.

    It is present as a monomer in the asymmetric unit of the unit cell of the crystal structure:

    NB7852A_Fig1_monomer.png

    Crystal packing analysis suggests that the stable oligomeric form in solution should be the following dimer:

    NB7852A_Fig2_dimer.png

     There appears to be a gene duplication in the protein with the N-terminal residues ~1-72 (magenta) having similar structure to residues ~73-126 (cyan) with a sequence identity of ~18% (two domains joined by a linker):

    NB7852A_Fig3_duplication.png

         

    FFAS detects sequence similarity between this protein and other solved protein strucutres with the following PDB ids: 2rbb (Crystal structure of a glyoxalase/bleomycin resistance protein/dioxygenase family enzyme from Burkholderia phytofirmans PsJN, FFAS score: -63.000, topsan page); 2p25 ( The crystal structure of the glyoxylase family protein from Enterococcus faecalis, FFAS Score: -56.300, topsan page); 1f9z (Crystal structure of the NI(II)-bound glyoxalase I from Escherichia coli, FFAS Score: -56.000) and other such proteins, Ref3).

         

    Based on FATCAT structural superimpositions, this protein is structurally similar to 2rbb (104 aligned residues, RMSD: 2.2 A, sequence identity: 17.0%), 2p25 (106 aligned residues, RMSD: 2.2 A, sequence identity: 16.8%), 1f9z (106 aligned residues, RMSD: 2.1 A, sequence identity: 20.5%), 2rk0 (108 aligned residues, RMSD: 2.1 A, sequence identity: 12.2%,), which also has a topsan page, 2c21 (104 aligned residues, RMSD: 1.9 A, sequence identity: 18.9%), and members of the Glyoxalase I (lactoylglutathione lyase) family from SCOP.

         

    There is unidentified ligand-like electron density (black, modeled as UNL) surrounded by amino acids His5, Phe39, Glu53, Arg57, His73, Asp107, Glu111 AND Glu123 which appears as if it could be putative active site formed by the dimer:

    NB7852A_Fig4_2_putativeactivesite.png

    Some of these amino acids are conserved in similar structures.  In the figure below,  this protein is shown in green, 2c21A is in cyan, 2p25A is in magneta, and 1f9zA is in pink.  Four conserved residues are shown in stick represention.  The labeling of these residues is based on the structure of this protein.  The corresponding residues in the other structures are listed in the table below.

    NB7852A_Figure5 (1).png

         

           this protein  2c21A 2p25A 1f9zA
     First conserved His  His5  His8  His8  His5
     First conserved Glu  Glu53  Glu59  Glu55  Glu56

     Second conserved His

     His73  His77  His76  His74
    Second conserved Glu Glu123 Glu120 Glu123 Glu122
     shown in  green  cyan  magetna  pink

         

    The E. coli glyoxalase I uses Ni(II) as cofactor, but other glyoxalases including eukaryotic/human ones are known to use Zn(II). Known substrates of glyoxalase I are methylglyoxal, glyoxal and acyclic alpha-oxoaldehydes (Ref4). Glyoxalase I appears to be of interest as a drug target (Ref4, Ref5).

    References:

    1)  Sukdeo N, Honek JF. Microbial glyoxalase enzymes: metalloenzymes controlling cellular levels of methylglyoxal. Drug Metabol Drug Interact. 2008;23(1-2):29-50.

    2)  Mannervik B. Molecular enzymology of the glyoxalase system. Drug Metabol Drug Interact. 2008;23(1-2):13-27.

    3) He MM, Clugston SL, Honek JF, Matthews BW. Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation. Biochemistry. 2000 Aug 1;39(30):8719-27.

    4)  Thornalley PJ. Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation.

    Biochem Soc Trans. 2003 Dec;31(Pt 6):1343-8. Review.

    5)  Ariza A, Vickers TJ, Greig N, Armour KA, Dixon MJ, Eggleston IM, Fairlamb AH, Bond CS. Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme. Mol Microbiol. 2006 Feb;59(4):1239-48.

     

     

    Ligand Summary

    Reviews

    References

     

    No references found.

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