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The Open Protein Structure Annotation Network
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3lou

    Table of contents
    1. 1. Protein Summary
      1. 1.1.  
    2. 2. Ligand Summary

    Title Crystal structure of Formyltetrahydrofolate deformylase (YP_105254.1) from BURKHOLDERIA MALLEI ATCC 23344 at 1.90 A resolution. To be published
    Site JCSG
    PDB Id 3lou Target Id 398529
    Molecular Characteristics
    Source Burkholderia mallei atcc 23344
    Alias Ids TPS29648,YP_105254.1, _0004.004077_, 327757 Molecular Weight 32792.00 Da.
    Residues 291 Isoelectric Point 6.39
    Sequence msvpqrphqfvltlscpsaagqvaavvglldrhrcyvdeltvfdddlsarffvrcvfhatddadalrvd alrrefepiaerfrmqwaihdvaarpkvlimvsklehcladllfrwkmgelkmdivgivsnhpdfapla aqhglpfrhfpitadtkaqqeaqwldvfetsgaelvilarymqvlspeasarlanrainihhsflpgfk gakpyhqahargvkligatahfvtddldegpiieqvvervdhsyrpeqllavgrdvecitlaravkafi errvflngdrtvvfq
      BLAST   FFAS

    Structure Determination
    Method XRAY Chains 4
    Resolution (Å) 1.90 Rfree 0.221
    Matthews' coefficent 2.59 Rfactor 0.185
    Waters 870 Solvent Content 52.43

    Ligand Information
    Ligands
    Metals

    Jmol

     
    Google Scholar output for 3lou
    1. Identification of two-histidines one-carboxylate binding motifs in proteins amenable to facial coordination to metals
    B Amrein, M Schmid, G Collet, P Cuniasse, F Gilardoni - Metallomics, 2012 - xlink.rsc.org
     
    2. Crystal structure of tandem ACT domain_containing protein ACTP from Galdieria sulphuraria
    E Bitto, DJ Kim, CA Bingman, HJ Kim - Proteins: Structure, , 2012 - Wiley Online Library
     

    Protein Summary

    The structure of target ID 398529 was determined to a resolution of 1.9 Angstroms using two wavelength Se-MAD phasing. Shown below is a ribbons representation of the structure of the monomer color coded with the N-terminal end in blue and the C-terminal end in red. The structure consists of two domains. The larger C-terminal structural domain corresponds to residues 95-291. This C-terminal domain coincides with the Pfam family Formyl_trans_N (PF00551). Current annotations suggest that this target is an enzyme catalyzes the third step of de novo purine biosynthesis, phosphoribosylglycinamide formyltransferase (EC 2.1.2.2).

    monomer.png

     

    Shown below is the biochemical reaction catalyzed by EC 2.1.2.2

    R04325.bmp

     

     

     

     

     

    A search of the Pfam database using the sequence of target ID 398529 reveals there are 69 structures in the PDB that belong to the Formyl_trans_N family. A portion of the  amino acid sequence of the N-terminal region of target ID 398529 (i.e. residues 11-66) shows a limited (Pfam A search E-value=0.005) to the ACT (PF01842) Pfam group. This family of domains generally have a regulatory role. ACT domains are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. Even though the amino acid sequence of the N-terminal domain only suggests the N-terminal domain belongs to the ACT Pfam group, the crystal structure of the of the N-terminal domain provides further evidence that the N-terminal domain of target ID 398529 performs the regulatory functions associated with a member of the ACT Pfam group. A search of the SCOP database using the fastSCOP Evolutionary Classification search engine reveals that the N-terminal domain of target ID 398529 is a member of the ACT-like suoerfamily , whose members show a ferredoxin-like fold. The structure of target ID 398529 is likely to represent one of the few examples of a ACT-like domain fused to a Formyl_N-transferase domain.

     

     

     

     

     

    The crystal structure along with the results of analytical size exclusion chromatography indicate that the tetramer is a significant oligomerization state. Shown below is a ribbons representation of the tetramer with the indivdual chains represented in different colors. The tetramer shows two pairs on monomers (blue and red) and (green and yellow). Within the structure of each pair the N-terminal domains show close range interactions whereas the C-terminal domains with these pairs are positioned to interact with the C-terminal domains on the other pair of monomers.

    tetramer.png

     

    The results of an  EBI-SSM structural similarity search using the coordinates of target ID 398529 are tabulated below

     

    PDB ID SSM-Z Score RMSD (Angstroms) Aligned Residues Total Residues in PDB ID % Sequence ID Description
    2ywr 10.9 1.66 191 216 27 CRYSTAL STRUCTURE OF GAR TRANSFORMYLASE FROM AQUIFEX AEOLICUS
    1c3e 10.4 1,70 188 210 22 NEW INSIGHTS INTO INHIBITOR DESIGN FROM THE CRYSTAL STRUCTURE AND NMR STUDIES OF E. COLI GAR TRANSFORMYLATE IN COMPLEX WITH BETA-GAR AND 10-FORMYL-5,8,10-TRIDEAZAFOLIC ACID
    1cde 10.4 1.75 189 210 22 STRUCTURES OF APO AND COMPLEXED ESCHERICHIA COLI GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE
    1mej 9.9 1.89 188 201 23 HUMAN GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE DOMAIN AT PH 8.5
    1men 9.5 2.02 191 201 23 COMPLEX STRUCTURE OF HUMAN GAR TFASE AND SUBSTRATE BETA-GAR
    3da8 9.0 1.93 188 205 22 CRYSTAL STRUCTURE OF PURN FROM MYCOBACTERIUM TUBERCULOSIS

     

    Shown below is a comparison of the crystal structures of target ID 398529 (green) and PDB ID 1cde (blue). The blue structure represents E. coli glycinamide ribonucleotide transformylase complexed with glycinamide ribonucleotide (magenta) and 5-deazafolic acid (red).

    1cde_comparison.png

     

     

     

    Shown below is a comparison of the region surrounding the 10-formyltetrahydrofolate binding site from the structure of the E. coli GAR Tfase (PDB ID 1cde, blue), A substrate analog of 10-formyltetrahydrofolate,5-deazafolic acid (labeled DZT) is shown.  Superimposed on the E. coli enzyme is the structure of target ID 398529 (green). A sulfate molecule from the crystallization solution, observed in the structure, is labed SO4. An Unknown Ligand (UNL) was modeled in one of the four subunits of target ID 398529. The position of the UNL corresponds to that of the DZT substrate anolog in PDB ID 1cde

    deazafolic_comparison.bmp

     

     

     

    Shown below is a comparison of the structures of target ID 398529(green) and the E. coli. GAR Tfase (PDB ID 1cde) in the vicinity of the bound substrate glycinamide ribonucleotide (GAR) and the tetrahydrofolate analog 5-deazafolic acid (DZT).  A sulfate molecule (SO4) from the crystallization was observed near the putative GAR binding site in the structure target ID 398529

    active_site_comparison.bmp

     

    References

    Almassy, R.J., Janson, C.A., Kan, C.C., and Hostomska, Z. (2002) "Structures of apo and complexed Escherichia coli glycinamide ribonucleotide transformylase" Proc. Natl. Acad. Sci. USA. 89:6114-6118.

     

    Dahms, T.E., Sainz, G., Giroux, E.L., Caperelli, C.A. and Smith, J.L. (2005) "The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase" Biochemistry Jul 26;44(29):9841-50.


    Greasley, S.E., Yamashita, M.M., Cai, H., Benkovic, S.J., Boger, D.L., Wilson, I.A. (1999) "New insights into inhibitor design from the crystal structure and NMR studies of Escherichia coli GAR transformylase in complex with beta-GAR and 10-formyl-5,8,10-trideazafolic acid." Biochemistry Dec 21; 38(51) 16783-93.

     

    Zhang, Y., Desharnais, J., Greasley, S.E., Beardsley, G.P., Boger, D.L., and Wilson, I.A. (2002) "Crystal structures of human GAR Tfase at low and high pH and with substrate beta-GAR." Biochemistry Dec 3;41(48):14206-15.

     

     

    Zhang, Z., Caradoc-Davies, T.T., Dickson, J.M., Baker, E.N., and Squire, C.J.,(2009) "Structures of glycinamide ribonucleotide transformylase (PurN) from Mycobacterium tuberculosis reveal a novel dimer with relevance to drug discovery." J. Mol. Biol. Jun 19l 389(4) 722-33.

     

     

     

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    Ligand Summary

    Reviews

    References

     

    No references found.

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