X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880

Verfasser / Beitragende:
[Babu A. Manjasetty, Frank H. Niesen, Heinrich Delbrück, Frank Götz, Volker Sievert, Konrad Büssow, Joachim Behlke, Udo Heinemann]
Ort, Verlag, Jahr:
2004
Enthalten in:
Biological Chemistry, 385/10(2004-10-01), 935-942
Format:
Artikel (online)
ID: 378941062
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024 7 0 |a 10.1515/BC.2004.122  |2 doi 
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245 0 0 |a X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880  |h [Elektronische Daten]  |c [Babu A. Manjasetty, Frank H. Niesen, Heinrich Delbrück, Frank Götz, Volker Sievert, Konrad Büssow, Joachim Behlke, Udo Heinemann] 
520 3 |a 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. 
540 |a © Walter de Gruyter 
690 7 |a Biochemistry  |2 nationallicence 
690 7 |a Molecular biology  |2 nationallicence 
690 7 |a Cellular biology  |2 nationallicence 
690 7 |a fumarylacetoacetate hydrolase family  |2 nationallicence 
690 7 |a hereditary tyrosinemia type I  |2 nationallicence 
690 7 |a metal-binding site  |2 nationallicence 
690 7 |a protein structure  |2 nationallicence 
690 7 |a structural genomics  |2 nationallicence 
690 7 |a X-ray crystallography  |2 nationallicence 
700 1 |a Manjasetty  |D Babu A.  |u 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  |4 aut 
700 1 |a Niesen  |D Frank H.  |u 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  |4 aut 
700 1 |a Delbrück  |D Heinrich  |u Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Institut für Chemie/Kristallographie, Freie Universität Berlin, Takustr. 6, D-14195 Berlin, Germany  |4 aut 
700 1 |a Götz  |D Frank  |u Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Alpha-Bioverfahrenstechnik GmbH, Heinrich-Hertz-Str. 1b, D-14532 Kleinmachnow, Germany  |4 aut 
700 1 |a Sievert  |D Volker  |u Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany  |4 aut 
700 1 |a Büssow  |D Konrad  |u Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany  |4 aut 
700 1 |a Behlke  |D Joachim  |u Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13092 Berlin, Germany  |4 aut 
700 1 |a Heinemann  |D Udo  |u 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  |4 aut 
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950 |B NATIONALLICENCE  |P 700  |E 1-  |a Manjasetty  |D Babu A.  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Niesen  |D Frank H.  |u 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  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Delbrück  |D Heinrich  |u Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Institut für Chemie/Kristallographie, Freie Universität Berlin, Takustr. 6, D-14195 Berlin, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Götz  |D Frank  |u Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Alpha-Bioverfahrenstechnik GmbH, Heinrich-Hertz-Str. 1b, D-14532 Kleinmachnow, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Sievert  |D Volker  |u Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Büssow  |D Konrad  |u Protein Structure Factory, Heubnerweg 6, D-14059 Berlin, Germany and Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, D-14195 Berlin, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Behlke  |D Joachim  |u Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, D-13092 Berlin, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Heinemann  |D Udo  |u 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  |4 aut 
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