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The Open Protein Structure Annotation Network
PDB Keyword
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3rza

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

    Title Crystal structure of a tripeptidase (SAV1512) from STAPHYLOCOCCUS AUREUS MU50 at 2.10 A resolution. To be published
    Site JCSG
    PDB Id 3rza Target Id 375153
    Molecular Characteristics
    Source Staphylococcus aureus subsp. aureus mu50
    Alias Ids TPS20115,NP_372036.1, 3.40.630.10, 104182 Molecular Weight 40194.62 Da.
    Residues 377 Isoelectric Point 4.94
    Sequence mineqrllntflelvqidsetgnestiqpilkekfialgldvkedeaakhpklgannlvctmnstieeg evpklyltshmdtvvpainvkpivkddgyiysdgttilgaddkaglaamlevlqvikeqqiphgqiqfv itvgeesgligakelnselldadfgyaidasadvgttvvgaptqmlisakiigktahastpkegvsain iaakaisrmklgqvdeittanigkfhggsatnivadevileaearshdperiktqvkhmtdvfettase lggkaevtveqsypgfkindneavvkiaqesarnlglsantiisgggsdgsiintfgipsvilgvgyek ihttnermpikslnllasqvleiikivarqsk
      BLAST   FFAS

    Structure Determination
    Method XRAY Chains 2
    Resolution (Å) 2.10 Rfree 0.2123
    Matthews' coefficent 2.30 Rfactor 0.1668
    Waters 397 Solvent Content 46.43

    Ligand Information
    Ligands
    Metals

    Jmol

     

    Protein Summary

    Target 375153 (JCSG target accession code HP2219D, GenBank accession code NP_372036.1) is a 377-residue protein from Staphylococcus aureus mu50 [Ref], (TAXON:158878) a strain of methicillin-resistant Staphylococcus aureus (MRSA) that is also resistant to vancomycin, which is an antibiotic that has traditionally been known as a drug of last resort when other antibiotic options have been exhuasted.

    Target 375153 is annotated as a metallopeptidase belonging to PFAM:PF01546, which includes a wide range of zinc metallopeptidases.

    The structure of target 375153 was solved by the Se-MAD method to a resolution of 2.10 Angstroms and reveals an alpha/beta fold that can be classifed as belonging to the Zn-dependent exopeptidase superfamily in the SCOP classification scheme (Figure 1).

    The fold contains two structural domains:  domain 1 comprises residues 1-180 and 290-375 while domain 2 consists of residues 181-289.  In this family of peptidases, domain 1, which contains two zinc ions at the active site, acts as the catalytic domain while domain 2 serves as a dimerization domain (Pfam PF07687) (Figure 1b).

     

    Figure 1.  Structure of target 375153 monomer: (a) gradiently colored from the N- (blue) to the C-terminus (red) and (b) showing the catalytic (green) and dimerization (purple) domains.  Zinc ions are represented as gray spheres.

    (a)

    HP2219D-gradient.png

     (b)

    HP2219D-domains.png

     

    Crystal packing and PISA analyses support that the functional oligomeric state of target 375153 is a dimer, consistent with other members of this metallopeptidase family (Figure 2).

    Figure 2.  Quaternary structure of target 375153 is a dimer.  Monomers A and B are colored orange and blue, respectively, and zinc ions are represented as gray spheres.  (a) and (b) are orthogonal views. 

    (a)

    HP2219D-oligomer.png

    (b)

    HP2219D-oligomer2.png

     

    A DALI search yields a number of structural neighbors that are peptidases (Table 1), with the top match being a peptidase (PepT) from Bacillus cereus, with an r.m.s.d of 1.5 Angstroms over 371 C-alpha atoms and a high sequence identity of 55% (PDB id 3gb0, TOPSAN).  A superposition of target 375153 with its top 3 structural neighbors, which are all peptidases, shows the folds to be very similar (Figure 3).

     

    Table 1. Top structural neighbors of target 375153 as assessed by DALI.

    N PDB Z-score RMSD LALI NRES %ID TITLE
    1 3gb0 53.3 1.5 371 373 55 PEPTIDASE T (3gb0 TOPSAN)
    2 1vix 42.4 2.4 355 410 25 PEPTIDASE T [Ref]
    3 1fno 41.5 2.4 352 408 25 PEPTIDASE T [Ref]
    4 3ife 39.5 3.5 356 416 23 PEPTIDASE T
    5 1cg2 36.8 3.4 361 389 22 CARBOXYPEPTIDASE G2 [Ref]
    6 1vgy 34.4 3.0 347 375 21 SUCCINYL-DIAMINOPIMELATE DESUCCINYLASE [Ref]
    7 2qyv 33.1 2.9 342 470 17 XAA-HIS DIPEPTIDASE (2qyv TOPSAN)
    8 2rb7 32.7 2.5 334 360 20 PEPTIDASE, M20/M25/M40 FAMILY (2rb7 TOPSAN)
    9 3ic1 32.0 5.0 339 370 19 SUCCINYL-DIAMINOPIMELATE DESUCCINYLASE
    10 3isz 31.8 5.5 337 369 20 SUCCINYL-DIAMINOPIMELATE DESUCCINYLASE

     

    Figure 3.  Superposition of target 375153 (yellow) with top 3 DALI matches: PDB id's 3gb0 (blue), 1vix (red), and 1fno (green).  Zinc ions are represented as spheres.

    HP2219D-superpose.png

     

    Figure 4.  Putative active site of target 375153 showing the zinc ions (gray spheres) and their ligands.  Distances (in Angstroms) between the zincs and their ligands are labeled.  Zinc coordination by Asp110 requires the peptide bond between this residue and Asp111 to be in the cis-configuration.

    HP2219D-activesite.png

     

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    Ligand Summary

    Reviews

    References

     

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