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The Open Protein Structure Annotation Network
PDB Keyword
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3f7w

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

    Title Crystal structure of putative fructosamine-3-kinase (YP_290396.1) from THERMOBIFIDA FUSCA YX-ER1 at 1.85 A resolution. To be published
    Site JCSG
    PDB Id 3f7w Target Id
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    Molecular Characteristics
    Source
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    Alias Ids
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    TPS1775,TFUS_04MAR05_CONTIG93_REVISED_GENE318, 87528
    Molecular Weight
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    Da.
    Residues
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    Isoelectric Point
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    Sequence
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      BLAST   FFAS

    Structure Determination
    Method XRAY
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    Chains 1
    Resolution (Å)
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    Rfree
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    Matthews' coefficent 2.68 Rfactor 0.165
    Waters
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    Solvent Content 54.12

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    Ligand Information
    Ligands
    Metals

    Jmol

     
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    Google Scholar output for 3f7w
    1. Design principles underpinning the regulatory diversity of protein kinases
    K Oruganty, N Kannan - Transactions of the Royal , 2012 - rstb.royalsocietypublishing.org
     

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    Protein Summary

    The protein encoded by Tfu2340 is the first structurally solved fructosamine kinase, a member of the Protein Kinase-Like (PKL) superfamily and fold. Accordingly, top hits from SSM (PDB codes: 2ppq, 2bkk and 1l8t) DALI (2qg7E and 2pulA) and FATCAT (1zylA) identified several PKL kinases as the most structurally similar proteins. This is confirmed by strong hits to Pfam03881, COG3001 and custom HMMs from a recent classification of PKLs (Natarajan et al). Fructosamine Kinases are found in eubacteria and eukaryotes, including human, where they act to tag aged glycated proteins for deglycoation and repair.

    The biomolecule of  Tfu2340 is a monomer as suggested by interface calculation. Analysis of its genomic neighborhood indicates functional associations with Tfu_2341 (protein-tyrosine-phosphatase) and Tfu_0696 (Putative 6-phosphofructokinase).


     
    The superposition with 2ppq and 2bbk are shown as below. Green: 387095, Purple: 2ppq, cyan: 2bbk.

    Structural Overview

    The FruK structure does not have high overall similarity to any previously solved structure in the CAK group. Of the various CAK structures available, it appears to be most similar to HSK2 and MTRK, but only by a small margin. This result is consistent with the previous classification of FruK as a distinct family within the CAK-like kinases (Kannan, Taylor et al. 2007):

    Table 1: Comparison of CAK-group kinases to FruK
    Structure    Dali Z-score    RMSD    Aligned Pos.    %ID
    HSK2    16.6    3.6    248    14
    MTRK    16    4.5    249    15
    CAK-chl    15    3.7    238    14
    Ytaa    14.6    4.5    251    15
    ChoK    14.5    3.4    230    14
    APH    12.6    4.3    211    18

    The overall structure of FruK is consistent with that of other structures in the CAK group (Scheeff and Bourne 2005; Kannan, Taylor et al. 2007). The distinctive insertion between helix E and the catalytic loop (PKA conventions are used here) is present in FruK.  FruK contains the standard two helices that form the core of this unit (Scheeff and Bourne 2005), and also displays a distinctive insertion of a small two-strand beta sheet (Figure 4) near the beginning of the insert.  The distinctive c-terminal structure also seen in CAKs is present in FruK, in a typical form (Figure 4).


    Figure 4: Comparison of FruK, HSK2, and APH structures. The distinctive structures seen in CAKs are highlighted, with the insert between helix E and the catalytic loop in blue and the c-terminal structure in yellow.  The additional insert seen in the helix E-catalytic loop insert in FruK is colored orange.

    ATP Binding Pocket / Catalytic Residues

    At the level of the ATP binding pocket and catalytic residues, FruK displays and amalgam of features seen in various other CAKs. Remarkably, the most similar ATP binding pocket is seen in APH, a CAK with a low overall similarity to FruK relative to other group members (see Table 1). Many CAKs interact with the adenine ring of ATP with an aromatic side chain, often via a ring stacking arrangement. APH distinctively forms this interaction with Y42 from strand 3, while other CAK structures form the interaction with a side chain from the linker region between the two lobes. FruK has a similar residue to APH in the form of F42 from strand 3. But remarkably, it also contains the aromatic residue in the linker region as well (W90). Thus, it looks to have used a mixture of methods seen in CAKs for adenine binding. Since ATP is unavailable in the structure, it is unclear if the specific positioning of ATP is more similar to APH or other CAKs.

    The remainder of the ATP-binding pocket also displays a remarkable degree of similarity to APH. A key ion pair (K/R-E) is present in most PKL kinases that links strand 3 and helix C and provides a stabilized positively charged residue for interactions with the ATP phosphates (Scheeff and Bourne 2005). However, in some CAKs this ion pair is missing completely, and in others, both residues are present, but do not appear to form a close interaction. In both APH and FruK, a K-E ion pair is present (K44-E60 in FruK), with a close interaction between the residues (this type of architecture is typical for ePKs as well). Also, in many CAKs the DFG motif is replaced with DxE (residues other than E are also seen, but the common characteristic is that the small G residue is replaced with a substantially larger one (Kannan, Taylor et al. 2007)). However, both APH and FruK retain a small reside at the third position of the motif (A212 in FruK). It is possible that retention of this residue correlates with the retention of the closely linked K-E ion pair. In any event, it is clear that the ATP binding pockets of APH and FruK share distinctive features that set them apart from other CAKs.

    The remainder of the ATP binding / catalytic region displays the normal features present in the CAKs, and the PKL superfamily. The key residues for metal binding and catalysis are present and appropriate orientations. The highly conserved H-bonding network that stabilizes the catalytic loop of many PKL kinases (Scheeff and Bourne 2005) is also present.


    Ligand Summary

    Cl and PEG6000 fragment (PEG) from crystallization, and EDO from cryo condition were modeled.


    References

    Reviews

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