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3p1v

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

    Title Crystal structure of a metallo-endopeptidases (BACOVA_00663) from Bacteroides ovatus at 1.93 A resolution. To be published
    Site JCSG
    PDB Id 3p1v Target Id 416711
    Molecular Characteristics
    Source Bacteroides ovatus atcc 8483
    Alias Ids TPS33814,ZP_02063708.1, 327424 Molecular Weight 46436.06 Da.
    Residues 406 Isoelectric Point 5.98
    Sequence qnfadyfqnktlrvdyiftgdatqqaiyldelsqlptwagrqhhlselplegngqiivkdlaskqciyq tsfsslfqewlstdeaketakgfentfllpypkqpvevevtlysprkktmatykhivrpddilihkrgv shitphrymlqsgnekdcidvailaegytekemdvfyqdaqrtceslfsyepfrsmkskfnivavasps tdsgvsvprenqwkqtavhshfdtfysdrylttsrvksvhnalagipyehiiilantdvyggggiynsy tlttahhpmfkpvvvhefghsfggladeyfydndvmtdtypldvepweqnistrvnfaskwkdmlpsga piptpiaekkkypvgvyegggysakgiyrpaydcrmktneypefcpvcqrairrmiefyvp
      BLAST   FFAS

    Structure Determination
    Method XRAY Chains 2
    Resolution (Å) 1.93 Rfree 0.207
    Matthews' coefficent 2.27 Rfactor 0.170
    Waters 756 Solvent Content 45.87

    Ligand Information
    Ligands
    Metals

    Jmol

     
    Google Scholar output for 3p1v
    1. The retinoid X receptors and their ligands
    MI Dawson, Z Xia - Biochimica et Biophysica Acta (BBA)-Molecular and , 2011 - Elsevier
     

    Protein Summary

    First structure of M64 metallopeptidase. This structure contains a N-terminal imminoglobin-like domain and a C-terminal domain which likely play a role in specificity. The C-terminal domain contains another zinc. Based on the structure, a region around within the C-terminal domain  is flexible and very likely play a role of trapping substrate (specificity loop). The N-terminal imminoglobin-like domain appears to have a unique topology, this needs to be examined more carefully.

     

    The IgA protease from Clostridium ramosum is longer and share the 2nd and 3rd domain (not the first domain). Highly homologous proteins are also present in other Bacteriodes species.

     

    This is a plan to experimentally verify that this protein can indeed use IgA as substrate (experiments had shown that this protein does not cleave IgA).

     

    Information about Bacteriodes infection: http://emedicine.medscape.com/article/233339-overview.

     

    Figure. 1. Structure of a putative Bacteriodes IgA peptidase

    sp13469a-1.png

    Fig 2. A highly restrictive active site defined by the C-terminal domain

    sp13469a-surf.png

     

    From Neil Rawlings:

    From: Neil Rawlings <ndr@sanger.ac.uk>
    To: Alex Bateman <agb@sanger.ac.uk>
    CC: Xu, Qingping <qxu@slac.stanford.edu>
    
    The known peptidase in M64 is from Clostridium ramosum and as part of 
    the infection process the peptidase inactives IgA.  There are several 
    bacterial toxins that do this, cleaving within the polyproline 
    hinge-region.  The Clostridium peptidase in particular cleaves Pro+Val 
    bonds in human IgA1 and IgA2 (Kosowska et al., 2002).  So there is no 
    surprise that a large domain from this structure is immunoglobulin-like, 
    interactions with this domain is presumably how the specificity is 
    restricted to IgA.  The structure of the peptidase domain is also not a 
    surprise, family M64 has been in the same clan as adamalysins probably 
    since it was created in MEROPS.  The catalytic zinc-binding motifs are 
    similar in both families.  The third catalytic zinc ligand in family M64 
    is Asp (within the motif HEXXHXXGXXD), which is more unusual (usually 
    His), but peptidases with Asp in this position have been crystallized 
    previously: snapalysin (MEROPS ID M07.001; PBD 1C7K, 1KUH), deuterolysin 
    (MEROPS ID M35.002; PDB 1EB6), peptidyl-Lys metalloendopeptidase (MEROPS 
    ID M35.004; PDB 1G12, 1GE5, 1GE6, 1GE7).
    
    The source organism for this protein is Bacteroides ovatus, which is a 
    normal human intestinal commensal.  Clostridium ramosum is also a 
    component of the normal human gut flora (as well as other human 
    cavities), and the IgA peptidase is only present in some strains 
    (Kosowska et al., 2002).  Clostridium ramosum can become pathogenic in a 
    number of diseases including appendicitis, liver abscesses, septicaemia, 
    mastitis.  I can find no mention of Bacteroides ovatus being pathogenic, 
    so why it would possess an IgA peptidase is an interesting question. 
    There are several families of IgA proteinases, including some with 
    different catalytic types (serine-type in MEROPS family S6), but none 
    have ever been crystallized before to my knowledge.  Cleaving at prolyl 
    bonds is unusual so understanding how the substrate binds would also be 
    interesting.  Is it possible to predict substrate binding pockets?
    
    Reference: Kosowska, K., Reinholdt‖, J., Rasmussen, L. K., Sabat, A., 
    Potempa, J., Kilian, M. & Poulsen, K. (2002) The Clostridium ramosum IgA 
    Proteinase Represents a Novel Type of Metalloendopeptidase.  J. Biol. 
    Chem. 277, 11987-11994.
    

    Ligand Summary

    Reviews

    References

     

    No references found.

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