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The Open Protein Structure Annotation Network
PDB Keyword
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3ffr

    Title Crystal structure of phosphoserine aminotransferase SerC (EC 2.6.1.52) (YP_677612.1) from CYTOPHAGA HUTCHINSONII ATCC 33406 at 1.75 A resolution. To be published
    Site JCSG
    PDB Id 3ffr Target Id 390729
    Molecular Characteristics
    Source Cytophaga hutchinsonii atcc 33406
    Alias Ids TPS20857,YP_677612.1, RER070207001728, 3.40.640.10, 332686 Molecular Weight 40384.30 Da.
    Residues 361 Isoelectric Point 7.06
    Sequence mnnkiyftpgpselyptvrqhmitaldekigvishrskkfeevyktasdnlktllelpsnyevlflasa teiweriiqncvekksfhcvngsfskrfyefagelgreaykeeaafgkgfypaditvpadaeiiclthn etssgvsmpvedintfrdknkdalifvdavsslpypkfdwtkidsvffsvqkcfglpaglgvwilndrv iekskallakrksigtyhtipsmlekarvnqtpetpnamnifllgkvtgdmlqisadgirkqteekaal intyiesskvfsfgvedaklrsmttivanttmlpgeinkilepfdmavgagygskketqirianfpahs leqvhklvqtlkekig
      BLAST   FFAS

    Structure Determination
    Method XRAY Chains 1
    Resolution (Å) 1.75 Rfree 0.162
    Matthews' coefficent 3.18 Rfactor 0.143
    Waters 395 Solvent Content 61.37

    Ligand Information
    Ligands
    Metals

    Jmol

     
    Google Scholar output for 3ffr
    1. PURIFICATION OF LYSINE DECARBOXYLASE: A MODEL SYSTEM FOR PLP ENZYME INHIBITOR DEVELOPMENT AND STUDY
    LC Zohner - 2011 - digitalcommons.unl.edu
     
    2. Crystal structure and substrate specificity of the thermophilic serine: pyruvate aminotransferase from Sulfolobus solfataricus
    C Sayer, M Bommer, M Isupov, J Ward - Section D: Biological , 2012 - scripts.iucr.org
     

    Protein Summary

    Gene CHU_0995 from Cytophaga hutchinsonii atcc 33406 encodes the YP_677612 protein, a phosphoserine aminotransferase enzyme from the family PF00266.

    Pre-SCOP classifies 3ffr in the alpha/beta class, PLP-dependent transferases superfamily. A SSM search for structural homologs returns several hits that are aminotransferases (see table below).

    SSM Structural Homologs
    N PDB Q-score RMSD TITLE
    1 2fyf 0.6557 1.632 STRUCTURE OF A PUTATIVE PHOSPHOSERINE AMINOTRANSFERASE FROM MYCOBACTERIUM TUBERCULOSIS
    2 2c0r 0.633 1.718 CRYSTAL STRUCTURE OF PHOSPHOSERINE AMINOTRANSFERASE FROM BACILLUS CIRCULANS VAR. ALKALOPHILUS AT PH 8.5
    3 2bhx 0.631 1.715 RADIATION DAMAGE OF THE SCHIFF BASE IN PHOSPHOSERINE AMINOTRANSFERASE (STRUCTURE A)
    4 1w23 0.6306 1.728 CRYSTAL STRUCTURE OF PHOSPHOSERINE AMINOTRANSFERASE FROM BACILLUS ALCALOPHILUS
    5 1bt4 0.6235 1.750 PHOSPHOSERINE AMINOTRANSFERASE FROM BACILLUS CIRCULANS SUBSP. ALKALOPHILUS
    6 1iug 0.6169 1.849 THE CRYSTAL STRUCTURE OF ASPARTATE AMINOTRANSFERASE WHICH BELONGS TO SUBGROUP IV FROM THERMUS THERMOPHILUS
    7 2dr1 0.6119 1.876 CRYSTAL STRUCTURE OF THE PH1308 PROTEIN FROM PYROCOCCUS HORIKOSHII OT3
    8 3e77 0.6075 1.746 HUMAN PHOSPHOSERINE AMINOTRANSFERASE IN COMPLEX WITH PLP
    9 2bkw 0.5613 2.135 YEAST ALANINE:GLYOXYLATE AMINOTRANSFERASE YFL030W
    10 2ch2 0.5491 1.923 STRUCTURE OF THE ANOPHELES GAMBIAE 3-HYDROXYKYNURENINE TRANSAMINASE IN COMPLEX WITH INHIBITOR
    11 2ch1 0.5472 1.906 STRUCTURE OF ANOPHELES GAMBIAE 3-HYDROXYKYNURENINE TRANSAMINASE
    12 1m32 0.5361 2.038 CRYSTAL STRUCTURE OF 2-AMINOETHYLPHOSPHONATE TRANSAMINASE
    13 1j04 0.5324 2.063 STRUCTURAL MECHANISM OF ENZYME MISTARGETING IN HEREDITARY KIDNEY STONE DISEASE IN VITRO
    14 2yri 0.5313 2.157 CRYSTAL STRUCTURE OF ALANINE-PYRUVATE AMINOTRANSFERASE WITH 2-METHYLSERINE
    15 2huu 0.5292 2.021 CRYSTAL STRUCTURE OF AEDES AEGYPTI ALANINE GLYOXYLATE AMINOTRANSFERASE IN COMPLEX WITH ALANINE
    16 2huf 0.5292 2.001 CRYSTAL STRUCTURE OF AEDES AEGYPTI ALANINE GLYOXYLATE AMINOTRANSFERASE
    17 2hui 0.529 2.022 CRYSTAL STRUCTURE OF AEDES AEGYPTI ALANINE GLYOXYLATE AMINOTRANSFERASE IN COMPLEX WITH GLYOXYLIC ACID
    18 2yrr 0.5243 2.119 HYPOTHETICAL ALANINE AMINOTRANSFERASE (TTH0173) FROM THERMUS THERMOPHILUS HB8
    19 2z9w 0.5193 2.102 CRYSTAL STRUCTURE OF PYRIDOXAMINE-PYRUVATE AMINOTRANSFERASE COMPLEXED WITH PYRIDOXAL
    20 1vjo 0.5173 2.161 CRYSTAL STRUCTURE OF ALANINE--GLYOXYLATE AMINOTRANSFERASE (ALR1004) FROM NOSTOC SP. AT 1.70 A RESOLUTION
    21 2z9v 0.5164 2.100 CRYSTAL STRUCTURE OF PYRIDOXAMINE-PYRUVATE AMINOTRANSFERASE COMPLEXED WITH PYRIDOXAMINE
    22 2z9u 0.5156 2.106 CRYSTAL STRUCTURE OF PYRIDOXAMINE-PYRUVATE AMINOTRANSFERASE FROM MESORHIZOBIUM LOTI AT 2.0 A RESOLUTION
    23 2z9x 0.5142 2.125 CRYSTAL STRUCTURE OF PYRIDOXAMINE-PYRUVATE AMINOTRANSFERASE COMPLEXED WITH PYRIDOXYL-L-ALANINE
    24 1h0c 0.5138 2.077 THE CRYSTAL STRUCTURE OF HUMAN ALANINE:GLYOXYLATE AMINOTRANSFERASE

     A superposition of these structures are shown below. The color scheme is 3ffr (green), 1bt4 (cyan), 1h0c (lightmagenta), 1iug (yellow), 1j04 (salmon), 1m32 (lightgrey), 1vjo (slate), 1w23 (orange), 2bhx (lime), 2bkw (deepteal), 2c0r (hotpink), 2ch1 (yelloworange), 2ch2 (violetpurple), 2dr1 (grey70), 2fyf (marine), 2huf (olive), 2hui (smudge), 2huu (teal), 2yri (dirtyviolet), 2yrr (wheat), 2z9u (deepsalmon), 2z9v (lightpink), 2z9w (aquamarine), 2z9x (paleyellow), 3e77 (limegreen).

    all.png

    The 3ffr structure consists of two domains as shown below.

    MG14498B2.png MG14498B_SER.png

    The residue lysine 190, situated between the two domains, is covalently bonded to a pyridoxal-phosphate  (PLP) group via a Schiff base, indicating that this is a PLP dependent aminotransferase. Adjacent to the PLP group (in yellow stick representation) there is some extra density suggesting the presence of the amino acid serine (yellow stick representation) which could be a precursor to the substrate/product phosphoserine molecule. An electron density from an unbiased map (density modified experimentally phased map) has been included in the figure to support the assignment of PLP and SER. The proximity of serine to the PLP suggests that the phosphate moiety from PLP can be transfered to the serine moiety to form phosphoserine.

    One of the reagents used in the crystallization of 3ffr is PEG-300. Several of these molecules are observed ordered in the structure.  A couple of PEG-300 molecules are situated around a lysine residue as shown in the figure below.

    Lys233.png  Lys331.png

     

    The likley biologically relevant oligomeric state of the 3ffr could be a dimer shown below.

    MG14498B_dimer.png

     

     

     

    References:

     

    • Vié N, Copois V, Bascoul-Mollevi C, Denis V, Bec N, Robert B, Fraslon C, Conseiller E, Molina F, Larroque C, Martineau P, Del Rio M, Gongora C.  Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells.  Mol Cancer. 2008 Jan 25;7:14.  PMID: 18221502 [PubMed - indexed for MEDLINE]
    • Hart CE, Race V, Achouri Y, Wiame E, Sharrard M, Olpin SE, Watkinson J, Bonham JR, Jaeken J, Matthijs G, Van Schaftingen E.  Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway.  Am J Hum Genet. 2007 May;80(5):931-7. Epub 2007 Mar 30.  PMID: 17436247 [PubMed - indexed for MEDLINE]
    • Helgadóttir S, Rosas-Sandoval G, Söll D, Graham DE.  Biosynthesis of phosphoserine in the Methanococcales.  J Bacteriol. 2007 Jan;189(2):575-82. Epub 2006 Oct 27.  PMID: 17071763 [PubMed - indexed for MEDLINE]
    • Ali V, Nozaki T.  Biochemical and functional characterization of phosphoserine aminotransferase from Entamoeba histolytica, which possesses both phosphorylated and non-phosphorylated serine metabolic pathways.  Mol Biochem Parasitol. 2006 Jan;145(1):71-83. Epub 2005 Oct 5. PMID: 16289358 [PubMed - indexed for MEDLINE]
    • Martens JW, Nimmrich I, Koenig T, Look MP, Harbeck N, Model F, Kluth A, Bolt-de Vries J, Sieuwerts AM, Portengen H, Meijer-Van Gelder ME, Piepenbrock C, Olek A, Höfler H, Kiechle M, Klijn JG, Schmitt M, Maier S, Foekens JA.  Association of DNA methylation of phosphoserine aminotransferase with response to endocrine therapy in patients with recurrent breast cancer.  Cancer Res. 2005 May 15;65(10):4101-17.  PMID: 15899800 [PubMed - indexed for MEDLINE]
    • Dubnovitsky AP, Ravelli RB, Popov AN, Papageorgiou AC.  Strain relief at the active site of phosphoserine aminotransferase induced by radiation damage.  Protein Sci. 2005 Jun;14(6):1498-507. Epub 2005 May 9.  PMID: 15883191 [PubMed - indexed for MEDLINE]
    • Dubnovitsky AP, Kapetaniou EG, Papageorgiou AC.  Enzyme adaptation to alkaline pH: atomic resolution (1.08 A) structure of phosphoserine aminotransferase from Bacillus alcalophilus.  Protein Sci. 2005 Jan;14(1):97-110.  PMID: 15608117 [PubMed - indexed for MEDLINE]
    • Dubnovitsky AP, Kapetaniou EG, Papageorgiou AC.  Expression, purification, crystallization and preliminary crystallographic analysis of phosphoserine aminotransferase from Bacillus alcalophilus.  Acta Crystallogr D Biol Crystallogr. 2003 Dec;59(Pt 12):2319-21. Epub 2003 Nov 27.  PMID: 14646107 [PubMed - indexed for MEDLINE]
    • Baek JY, Jun DY, Taub D, Kim YH.  Characterization of human phosphoserine aminotransferase involved in the phosphorylated pathway of L-serine biosynthesis.  Biochem J. 2003 Jul 1;373(Pt 1):191-200.  PMID: 12633500 [PubMed - indexed for MEDLINE]
    • Ho CL, Saito K.  Molecular biology of the plastidic phosphorylated serine biosynthetic pathway in Arabidopsis thaliana.  Amino Acids. 2001;20(3):243-59. Review.  PMID: 11354602 [PubMed - indexed for MEDLINE]
    • Basurko MJ, Marche M, Darriet M, Cassaigne A.  Phosphoserine aminotransferase, the second step-catalyzing enzyme for serine biosynthesis.  IUBMB Life. 1999 Nov;48(5):525-9.  PMID: 10637769 [PubMed - indexed for MEDLINE]
    • Hester G, Stark W, Moser M, Kallen J, Marković-Housley Z, Jansonius JN.  Crystal structure of phosphoserine aminotransferase from Escherichia coli at 2.3 A resolution: comparison of the unligated enzyme and a complex with alpha-methyl-l-glutamate.  J Mol Biol. 1999 Feb 26;286(3):829-50.  PMID: 10024454 [PubMed - indexed for MEDLINE]
    • Ho CL, Noji M, Saito M, Yamazaki M, Saito K.  Molecular characterization of plastidic phosphoserine aminotransferase in serine biosynthesis from Arabidopsis.  Plant J. 1998 Nov;16(4):443-52.  PMID: 9881164 [PubMed - indexed for MEDLINE]
    • Melcher K, Rose M, Künzler M, Braus GH, Entian KD.  Molecular analysis of the yeast SER1 gene encoding 3-phosphoserine aminotransferase: regulation by general control and serine repression.  Curr Genet. 1995 May;27(6):501-8.  PMID: 7553933 [PubMed - indexed for MEDLINE]
    • Ouzounis C, Sander C.  Homology of the NifS family of proteins to a new class of pyridoxal phosphate-dependent enzymes.  FEBS Lett. 1993 May 10;322(2):159-64.  PMID: 8482384 [PubMed - indexed for MEDLINE]
    • Snell K.  Enzymes of serine metabolism in normal and neoplastic rat tissues.  Biochim Biophys Acta. 1985 Dec 13;843(3):276-81.  PMID: 3933573 [PubMed - indexed for MEDLINE]

    Reviews

    References

     

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