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

    Title Structures of the first representatives of Pfam family PF06938 (DUF1285) reveal a new fold with repeated structural motifs and possible involvement in signal transduction. Acta Crystallogr.,Sect.F 66 1218-1225 2010
    Site JCSG
    PDB Id 2re3 Target Id 374660
    Molecular Characteristics
    Source Silicibacter pomeroyi dss-3
    Alias Ids TPS1631,YP_165412.1, PF06938, 285601 Molecular Weight 21243.11 Da.
    Residues 193 Isoelectric Point 5.66
    Sequence msgqkpvkpsadgllasaraikskgpapvhlwnppfngdidmriardgtwfyqgtpinrpamvrlfssi lkreedrfylvtpvekvgirvddapfvavdvevagqgrkqvltftthvgdsavagegnpirmaqdpatg epapyvhvraglealidrksfyrlmdlgeiedgwfglwssgsffplmtveelerg
      BLAST   FFAS

    Structure Determination
    Method XRAY Chains 2
    Resolution (Å) 2.50 Rfree 0.258
    Matthews' coefficent 3.00 Rfactor 0.215
    Waters 189 Solvent Content 59.02

    Ligand Information


    Google Scholar output for 2re3
    1. Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard
    TC Terwilliger, PD Adams, RJ Read - Section D: Biological , 2009 - scripts.iucr.org
    2. Structural classification of proteins and structural genomics: new insights into protein folding and evolution
    A Andreeva, AG Murzin - Acta Crystallographica Section F: Structural , 2010 - scripts.iucr.org
    3. Bacterial pleckstrin homology domains: a prokaryotic origin for the PH domain
    Q Xu, A Bateman, RD Finn, P Abdubek - Journal of molecular , 2010 - Elsevier
    4. Structures of the first representatives of Pfam family PF06938 (DUF1285) reveal a new fold with repeated structural motifs and possible involvement in signal
    GW Han, C Bakolitsa, MD Miller, A Kumar - Section F: Structural , 2010 - scripts.iucr.org
    5. Distributed structure determination at the JCSG
    H van den Bedem, G Wolf, Q Xu - Section D: Biological , 2011 - scripts.iucr.org

    Protein Summary

    The SPO0140 gene from Silicibacter pomeroyi encodes the YP_165412 protein, a member of the protein family PF06938 (DUF1285), which is an uncharacterized family of bacterial proteins (COG3816). SPO0140 (PDB id: 2re3) and Sbal_2486 (PDB id: 2ra9) provide the first structural representatives of this family. SPO0140 genomic context (SPO0025, hypothetical hydrolase from the NUDIX family and SPO0026, a polyA polymerase family protein) indicates functional association (score 0.63) with nucleic acid processing enzymes.


    The 2re3 structure reveals a PH-like domain with some structural similarity to proteins that bind DNA or RNA (1prk, 1l3a, 2gia) or negatively charged oligosaccharides  (PDB:1plf). SPO0140 is an a/b protein comprising two domains (Fig. 1) both characterized by short helix-β-meander motifs. Each β-meander is composed of three anti-parallel β-strands linked by hairpins to form a small sheet, while the intervening helices are oriented at right angles to one another. The N-terminal domain (residues 1-93) consists of two helix-meander motifs with the two β-meanders aligning along their edge to form a twisted mixed sheet. This arrangement is repeated in the C-terminal domain (residues 94-193) with an additional β-sheet packing up against one end of the six-stranded twisted mixed sheet to form a β-sandwich (Fig. 1).


    2re3_topFig1 (1).png


    Figure 1. Ribbon diagram of SPO0140. Rainbow color coding is from blue (N-terminus) to red (C-terminus) showing the N-terminal (right) and C-terminal (left) domains. Secondary structure elements are indicated.


    SPO0140 crystallized as a dimer with 2-fold symmetry. The dimer buries ~810 Å^2 of solvent-accessible surface per monomer and involves mainly helix H1, strand β1 and the H3-β4 loop from the N-terminal domain, helix H4 and strands β14-β15 from the C-terminal domain. Packing analysis (PISA) indicates that a dimer is the likely biologically relevant form.


    [Look at conservation of residues implicated in dimerization interface]


    A structural superposition of SPO0140 with Sbal_2486 (PDB id: 2ra9), another member of the DUF1285 family, shows an r.m.s.d of 2.4 Å over 146 residues with a sequence identity of 25% (Dali Z-scr=14). Structural elements missing from Sbal_2486 involve SPO0140 helices H1 and H2 and part of strand β1, as well as the C-terminal β-meander and helix H6 (Fig. 2A). Sbal_2486 crystallized as a monomer, suggesting that the missing regions could be necessary for dimer formation.


    [In addition to dimerization, the missing elements are also involved in the formation of the likely binding cavities (see below)].


    A search with FATCAT using both domains of SPO0140 revealed weak similarity to a small number of structures with diverse functions, perhaps sharing in common binding to a negatively-charged ligand (sugar-binding platelet activation factor, transcriptional regulator, serine/threonine kinase, mitochondrial RNA binding protein). The closest similarity occurs with PA2021 from Pseudomonas aeruginosa (PDB id: 1ywy) over the C-terminal domain of SPO0140 with an r.m.s.d. of 3.4 Å over 67 residues and a sequence identity of 12% (Fig. 2B). Pre-SCOP classifies PA2021 as having a PH domain-like barrel capped by an alpha helix.


    A search using the N-terminal domain of SPO0140 returned a single weak hit with the RNA-recognition motif of polyadenylation element protein 3 (PDB id: 2dnl) with an r.m.s.d. of 3.1 Å over 47 residues and a sequence identity of 14%.







    Figure 2. Stereo ribbon diagrams showing the structural superposition of structures exhibiting similarity to SPO0140. (A) Superposition of SPO0140 (residues 10-192, PDB id: 2re3, in gray) with Sbal_2486 (residues 29-155, PDB id: 2ra9, in blue), another member of the DUF1285 family. (B) Superposition of the C-terminal domain of SPO0140 (residues 94-193, PDB id 2re3, in gray) with a member of the UPF0051 family (residues 23-96, PDB id 1ywy, in blue).


    In addition to a similarity with the UPF0051 family (PDB id: 1ywy), structural comparisons of the C-terminal domain indicate an involvement with the cytoskeleton. Top hits include the EVH1 domain from a mouse ENA/VASP-like protein (PDB id: 1qc6, r.m.s.d. 3.6 Å over 65 residues, 3% sequence identity), the human EVH1 domain from VASP (PDB id: 1egx, r.m.s.d. 3.5 Å over 64 residues, 7% sequence identity), the human EVH1 domain from mena (PDB id: 2iyb, r.m.s.d. 3.5 Å over 63 residues, 5% sequence identity). Except for sequence identity, these superposition values are very similar to the ones obtained for 1ywy. A superposition of the structures is shown in Fig. 3.


    [MoxR genetic context, repeated through DUF1285 family members, also has functional associations with metal binding and chaperones] 


    MATCH        + kG++PVhlWNPpF GD+DmrIa+DGTWFY+GTPI R ++VRLFS++L+r++D   +LVTPVEKVGIrVdDAPF+AV ++v G g +qVL+F T VgD + AG ++p+R + dp tge++PY+hVR++LEAL+ R  fY L +lGe     ++++fG +S G fFP++    


     N-terminal domain cavity (775 Å^3) residues:




    C-terminal domain cavity residues:


    Interdomain cavity residues:


    Dimer cavity residues:




    A search with CastP reveals two cavities, one in each domain. The N-terminal domain cavity (~775 Å^3) is hydrophobic

    [check electrostatics plot]

    and contains a number of solvent-exposed aromatics (W50, F51, Y52, F66) - also hydrophobic (L14, A20, I21, I40, I44, I57, V83, V86, I88) residues.


    [check conservation/alignments]


    The  C-terminal domain cavity (~675 Å^3) is of similar nature, containing a number of solvent-exposed hydrophobic and aromatic residues (P140, P142, F159, Y160, L162, W172, F173, L175, L184, L190).


    [FY motifs? Are the domains formed by gene duplication? Cavities are not found in 2ra9.]


    The largest cavity (~ 1590 Å^3) occurs along the two-fold symmetric dimerization interface (P26, A27, P28, V29, H30, S68, L70, R72, D119, S120, A121, V122, G124, G126, N127, H145, V146, R147, A148, G149, L150).




    The domain architecture of one DUF1285 homolog includes a member of the phosphoglycerate mutase family (PF00300) suggesting an involvement in carbohydrate metabolism.


    The genome context (STRING) of  DUF1285 members supports a role in (...). SPO0140 shows a high degree of confidence in a functional association with a member of the MoxR family of ATPases (SPO0139), proteins that have been suggested to act as molecular chaperones (Snider 2006)



    Ligand Summary





    No references found.

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