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    1. 1. Protein Summary
    2. 2. Ligand Summary

    Title Crystal structure of PanE/ApbA family ketopantoate reductase (YP_299159.1) from Ralstonia eutropha JMP134 at 2.15 A resolution. To be published
    Site JCSG
    PDB Id 3hwr Target Id 376637
    Molecular Characteristics
    Source Ralstonia eutropha jmp134
    Alias Ids TPS6973,YP_299159.1, 104105 Molecular Weight 31531.43 Da.
    Residues 299 Isoelectric Point 6.15
    Sequence mkvaimgagavgcyyggmlaragheviliarpqhvqaieatglrletqsfdeqvkvsassdpsavqgad lvlfcvkstdtqsaalamkpalaksalvlslqngvenadtlrslleqevaaavvyvatemagpghvrhh grgelvieptshganlaaifaaagvpvetsdnvrgalwaklilncaynalsaitqlpygrlvrgegvea vmrdvmeecfavaraegvklpddvalairriaetmpgqssstaqdlargkrseidhlnglivrrgdalg ipvpanrvlhalvrliedkqqhg
      BLAST   FFAS

    Structure Determination
    Method XRAY Chains 2
    Resolution (Å) 2.15 Rfree 0.226
    Matthews' coefficent 2.71 Rfactor 0.183
    Waters 214 Solvent Content 54.58

    Ligand Information


    Google Scholar output for 3hwr
    1. Detecting subtle functional differences in ketopantoate reductase and related enzymes using a rule-based approach with sequence-structure homology recognition
    S Mondal, C Nagao, K Mizuguchi - Protein Engineering Design , 2010 - Oxford Univ Press

    Protein Summary

    The structure of YP_299159.1 from Ralstonia eutropha jmp134  has been refined to a resolution of 2.15 Angstroms from a hexagonal crystal form, P6(1). Initial phasing was performed using Se-MAD at a resolution of 2.4 Angstroms and the 2.15 Angstrom refinement was restrained against the 2.4 Angstroms MAD phases.

    A search of the Pfam database using the sequence of YP_299159.1 shows that this target is comprised of two Pfam domains. The N-terminal domain (residues 3-150) belongs to the ketopantonoate reductase (PanE/ApbA) Pfam group (PF02558) The C-terminal domain (residues 170-293) belong to the ketopantonoate reductase (PanE/ApbA) Pfam group C terminal (PF08546). Lysine at postion 178 (K178) is expected to be the active side residue (by similarity).  The N-terminal domain belongs to the Rossmann Clan in Pfam. This enzyme  catalyses the reduction of keto pantoic to pantoic acid in the alternative pyrimidine biosynthetic (APB) pathway.


    Shown above is a ribbons representation of the structure of YP_299159.1. Crystal packing suggests that a significant oligomerization state in solution is a dimer. This dimer is represented above with the individual monomers in red and green respectively. NADPH, believed to be a cofactor, was added to the crystallization, and a molecule of NADPH is bound to each monomer in the crystal structure (red spheres). Also bound to the crystal structure on each monomer is a bicine molecule. Bicine was used as a buffer in the crystallization solutions.



    active_site (1).bmp















    Shown above is a representation of the putative active site region of YP_299159.1with the protein backbond in yellow. Some amino acid sidechains in short range contact distance with a bound NADPH cofactor ligand and bicine molecule (from the crystallization solutions) is shown superimposed on 2fo-fc omit electron density maps (blue).

    A search of the PDB database using the DALI server shows that the following structures are similar to that of YP_299159.1 The results of this search indicate that YP_299159.1 is similar in structure to ketopantoate reductase (EC an enzyme involved in the biosynthesis of Coenzyme A.



    Seq ID


    PDB ID Z-score

    Num Aligned


                                              Structure Description
       2.2 28 1yjq 33.3 283 Crystal structure of ketopantoate reductase in complex with NADP+
    2.0 29 3ghy 33.1 290 Crystal structure of a putative ketopantoate reductase from Ralstonia solanacearum MolK2
    2.1 28 1yon 33.1 292 Escherichia coli ketopantoate reductase in complex with 2-monophosphoadenosine-5'-diphosphate
    2.2 28 2ofp 32.9 282 Crystal structure of Escherichia coli ketopantoate reductase in a ternary complex with NADP+ and pantoate
    2.2 28 1ks9 32.3 281  Ketopantoate Reductase from Escherichia coli
    2.2 21 3ego 32.0 284 Crystal structure of Probable 2-dehydropantoate 2-reductase panE from Bacillus Subtilis
    2.3 20 3g17 31.0 280 Structure of putative 2-dehydropantoate 2-reductase from staphylococcus aureus
     4.3 28 2ew2 30.1 295 Crystal Structure of the Putative 2-Dehydropantoate 2-Reductase from Enterococcus faecalis
    2.2 28 2qyt 28.8 269  Crystal structure of 2-dehydropantoate 2-reductase from Porphyromonas gingivalis W83





    Shown below are amino acid sequence alignments between YP_299159.1 and the sequences from top scoring related structures from the DALI search. This sequence alignment reveals that Arg 31 near the adenine ring of the bound NADPH cofactor is conserved in most of the structures. The sidechain of Lys 76, which is within electrostatic contact distance of the pyrophosphate moiety of the bound NADPH is strictly conserved. Asn 102 near the nicitonamide ring on the bound NADPH is also strictly conserved. Lys 178, located near the bound bicine in the YP_299159.1 is also strictly conserved. Asn 186, another sidechain near the bicine binding site is not as well conserved.


    align1 (1).bmp




    Shown below is a reprenstation of the superimposed structures of YP_299159.1 (green) and PDB ID 2ofp (cyan), the structure of ketopantonate reductase from E.coli complexed with NADPH and pantoate substrate. Conserved active site residues are labeled in italics for the E. coli protein. This comparison reveals that bicine in the structure of YP_299159.1 mimics the binding of the natural substrate.





     Lobley CM, Ciulli A, Whitney HM, Williams G, Smith AG, Abell C, Blundell TL.
    Biochemistry. 2005 Jun 28;44(25):8930-9. "The crystal structure of Escherichia coli ketopantoate reductase with NADP+bound."

    Ciulli A, Chirgadze DY, Smith AG, Blundell TL, Ab J Biol Chem. 2007 Mar 16;282(11):8487 Epub 2007 Jan 16. "Crystal structure of Escherichia coli ketopantoate reductase in a ternary complexwith NADP+ and pantoate bound: substrate recognition, conformational change, and cooperativity."

    Lobley CM, Ciulli A, Whitney HM, Williams G, Smith AG, Abell C, Blundell TL.
    Biochemistry. 2005 Jun 28;44(25):8930-9. "The crystal structure of Escherichia coli ketopantoate reductase with NADP+bound."

    Matak-Vinković D, Vinković M, Saldanha SA, Ashurst JL, von Delft F, Inoue T,
    Miguel RN, Smith AG, Blundell TL, Abell C. Biochemistry. 2001 Dec 4;40(48):14493-500. Crystal structure of Escherichia coli ketopantoate reductase at 1.7 A resolution and insight into the enzyme mechanism.


    Britton KL, Asano Y, Rice DW. Nat Struct Biol. 1998 Jul;5(7):593-601." Crystal structure and active site location of N-(1-D-carboxylethyl)-L-norvaline




    Ligand Summary




    No references found.

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