caa a22 4500 378941062 CHVBK 20180305123652.0 cr unu---uuuuu 161128e20041001xx s 000 0 eng 10.1515/BC.2004.122 doi (NATIONALLICENCE)gruyter-10.1515/BC.2004.122 X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880 [Elektronische Daten] [Babu A. Manjasetty, Frank H. Niesen, Heinrich Delbrück, Frank Götz, Volker Sievert, Konrad Büssow, Joachim Behlke, Udo Heinemann] The human protein FLJ36880 belongs to the fumarylacetoacetate hydrolase family. The X-ray structure of FLJ36880 has been determined to 2.2 Å resolution employing the semi-automated high-throughput structural genomics approach of the Protein Structure Factory. FLJ36880 adopts a mixed β-sandwich roll fold and forms homodimers in crystals as well as in solution. One Mg2+ ion is bound to each subunit of the dimeric protein by coordination to three carboxylate oxygens and three water molecules. These metal binding sites are accessible from the same surface of the dimer, partly due to the disorder of the undecapeptide stretch D29 to L39. The overall structure and metal binding site of FLJ36880 bear clear similarities to the C-terminal domain of the bifunctional enzyme HpcE from Escherichia coli C, fumarylacetoacetate hydrolase from Mus musculus and to YcgM (Apc5008) from E. coli 1262. These similarities provide a framework for suggesting biochemical functions and evolutionary relationships of FLJ36880. It appears highly probable that the metal binding sites are involved in an enzymatic activity related to the catabolism of aromatic amino acids. Two point mutations in the active-site of FAH, responsible for the metabolic disease hereditary tyrosinemia type I (HTI) in humans, affect residues that are structurally conserved in FLJ36880 and located in the putative catalytic site. © Walter de Gruyter Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence fumarylacetoacetate hydrolase family nationallicence hereditary tyrosinemia type I nationallicence metal-binding site nationallicence protein structure nationallicence structural genomics nationallicence X-ray crystallography nationallicence Manjasetty Babu A. Protein Structure Factory, c/o BESSY GmbH, Albert-Einstein-Str. 15, D-12489 Berlin, Germany and Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13092 Berlin, Germany aut Niesen Frank H. Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Institut für Medizinische Physik & Biophysik, Charité Universitätsmedizin Berlin, Ziegelstr. 5-9, D-10096 Berlin, Germany aut Delbrück Heinrich Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Institut für Chemie/Kristallographie, Freie Universität Berlin, Takustr. 6, D-14195 Berlin, Germany aut Götz Frank Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Alpha-Bioverfahrenstechnik GmbH, Heinrich-Hertz-Str. 1b, D-14532 Kleinmachnow, Germany aut Sievert Volker Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany aut Büssow Konrad Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany aut Behlke Joachim Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13092 Berlin, Germany aut Heinemann Udo Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13092 Berlin, Germany and Institut für Chemie/Kristallographie, Freie Universität Berlin, Takustr. 6, D-14195 Berlin, Germany aut Biological Chemistry Walter de Gruyter 385/10(2004-10-01), 935-942 1431-6730 385:10<935 2004 385 bchm https://doi.org/10.1515/BC.2004.122 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2004.122 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Manjasetty Babu A. Protein Structure Factory, c/o BESSY GmbH, Albert-Einstein-Str. 15, D-12489 Berlin, Germany and Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13092 Berlin, Germany aut NATIONALLICENCE 700 1- Niesen Frank H. Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Institut für Medizinische Physik & Biophysik, Charité Universitätsmedizin Berlin, Ziegelstr. 5-9, D-10096 Berlin, Germany aut NATIONALLICENCE 700 1- Delbrück Heinrich Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Institut für Chemie/Kristallographie, Freie Universität Berlin, Takustr. 6, D-14195 Berlin, Germany aut NATIONALLICENCE 700 1- Götz Frank Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Alpha-Bioverfahrenstechnik GmbH, Heinrich-Hertz-Str. 1b, D-14532 Kleinmachnow, Germany aut NATIONALLICENCE 700 1- Sievert Volker Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany aut NATIONALLICENCE 700 1- Büssow Konrad Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany aut NATIONALLICENCE 700 1- Behlke Joachim Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13092 Berlin, Germany aut NATIONALLICENCE 700 1- Heinemann Udo Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13092 Berlin, Germany and Institut für Chemie/Kristallographie, Freie Universität Berlin, Takustr. 6, D-14195 Berlin, Germany aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 385/10(2004-10-01), 935-942 1431-6730 385:10<935 2004 385 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter