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The Open Protein Structure Annotation Network
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3tc9

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

    Title Crystal structure of a Hypothetical hydrolase (BT_3476) from Bacteroides thetaiotaomicron VPI-5482 at 2.23 A resolution. To be published
    Site JCSG
    PDB Id 3tc9 Target Id 392961
    Molecular Characteristics
    Source Bacteroides thetaiotaomicron vpi-5482
    Alias Ids TPS20263,NP_812388.1, 384298 Molecular Weight 48636.64 Da.
    Residues 429 Isoelectric Point 5.48
    Sequence ckdnddatgdfdpnkpvvisefspkegglgtrmllygenfgsdiskikvtiggqdskvvgakgkslycv vpakaydgdiklsilndegeeianteanekfvyqkkmlvttflgtmydgntkydlkdgpfddcggfgga vwlsfdpknhnhlylvgeqhptrlidfekeyvstvysglskvrticwtheadsmiitndqnnndrpnny iltresgfkviteltkgqncngaethpingelyfnswnagqvfrydfttqettplftiqdsgwefhiqf hpsgnyayivvvnqhyilrsdydwktkrlttpyivcgqqgakdwvdgvgkkarmhaprqgtfvknpayk gssdeydfyfcdrenhciriltpqgrvttfagrgsngtsgyndgdlrqearfnhpegivydeerecffi gdrenrrirkigyee
      BLAST   FFAS

    Structure Determination
    Method XRAY Chains 2
    Resolution (Å) 2.23 Rfree 0.2055
    Matthews' coefficent 2.38 Rfactor 0.1610
    Waters 382 Solvent Content 48.25

    Ligand Information
    Ligands
    Metals

    Jmol

     
    Google Scholar output for 3tc9

    Protein Summary

     

     

    BT3476 is a 457AA protein, closely homologous to two other proteins whose structures were recently solved by JSCG: 3kya (40% with SEQid to BT3476) and 3hrp (22% seq id). All three are two domain proteins, with a 6-bladed beta propeller domain accompanied by a N-terminal beta-sheet domain with immunoglobulin-like greek-key fold. This domain structure seems to be pretty unique and we couldnt find any examples in PDB.

     

    Folds of those 3 related targets, unique in pdb, are very similar with the exception for 4 insertions, loop 217-225 around the central tunnel and 299-321 and 251-255 and 150-155. The central cavity, negatively charged and usually filled with some ligands  is empty in all three structures. The conserved HIS186 (HIS 183 in 3KYA, HIS 189 in #HRP) from these structures may play a role in binding of a metal ligand. In the current target it is a phosphate ion, in 3KYA it was a Zn ion. These histidines are placed on a blade no 2 near the 'exit' from the central channel, occupy a rather positively charged area which does interface a free space, filled here with the solvent. However, these histidines are not conserved even in relatively close homologs of each of the solved proteins, so their role in conserved function of these proteins is not clear.

    Couple of hydrogen bonds hold the -2 blade to the dimeric partner in the asymmetric unit. Waters seem to be equally distributed over the entire propeller surface, but the density around the central cavity is the highest. The N-terminal portion resembling a 'head' has 2 surfaces entirely without any ligand. This propeller belongs to the s.c. 'velcro' family, with N- and C-terminal portions closely connected by hydrogen network of neighbor beta-strands. There are couple of unique TYR clusters in the fold of each monomer. In one of them, located around the transition from the propeller to the beta-sheet head domain, an additional positive density is present, not allocated to any known ligand.

     

    We are now debating the possible function of these three proteins and their immediate family.  As we argue below, we think we could make the case that these proteins are receptors, with the C-terminal domain representing a main sensor domain and the N-terminal being an auxilliary ligand binding domain. While proteins with a similar 6-bladed propellers have various enzymatic functions, they typically have no extra ligand binding domains. 

     

    - the N-terminal immunoglobulin-like fold belongs to E set domains superfamily which are often found in cell surface receptors, for instance 1UAD (exocyst complex component Sec5), which belongs to GTP-binding proteins mediating the transmembrane signaling initiated by the occupancy of certain cell surface receptors, and two sugar-utilizing enzymes: Five-domain alpha-amylase from Bacillus Stearothermophilus (1QHO) and Maltose/acarbose complex cyclodextrin glycosyl transferase from Thermoanerobacterium thermosulfurigenes (3BMV).

    - C-terminal domain shows strong structure similarity with a sensor domain of Serine/threonine-protein kinase PknD from Mycobacterium tuberculosis (1RWI). FFAS-SCOP score is -35.500, -29.500 and -40.300 for 3TC9, 3KYA, and 3HRP respectively.

    - Despite  significant structure similarity found with enzymes with six-beta propeller folds, there is no similarity in local function related motifs. For instance,  peptidyl-alpha-hydroxyglycine alpha-amidating lyase (3FVZ) active site is formed by a Zn(II) ion coordinated by three histidine residues (HIS585, HIS690,HIS786) and 2Z2P (virginiamycin B lyase from Staphylococcus aureus)  the active site formed by a Mg(II) ion coordinated by HIS270, ASP127, GLU268, GLU284; sequence aliment and structure analysis didn’t show any conserved residues in the three structures solved by JCSG

    Ligand Summary

    Reviews

    References

     

    No references found.

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    Files (4)

    FileSizeDateAttached by 
     DELPHI-BOTTOM.png
    Delphi electrostatic potential on one surface
    352.05 kB00:21, 5 Aug 2011cbtrameActions
     DELPHI-TOP.png
    Delphi electrostatic potential on the opposite surface
    330.03 kB00:21, 5 Aug 2011cbtrameActions
     Yasara-SIDE.jpg
    Yasara generated hydrogen bond network as seen from the side
    692.37 kB00:36, 5 Aug 2011cbtrameActions
     Yasara-TOP.jpg
    Hydrogen bond network of the monomer as seen from the top
    695.73 kB00:36, 5 Aug 2011cbtrameActions
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