|
|
| Line 1: |
Line 1: |
| | | | |
| | ==X-ray structure of homo sapiens Fumarylacetoacetate hydrolase domain containing protein 1 (FAHD1) at 1.56A resolution.== | | ==X-ray structure of homo sapiens Fumarylacetoacetate hydrolase domain containing protein 1 (FAHD1) at 1.56A resolution.== |
| - | <StructureSection load='6foh' size='340' side='right' caption='[[6foh]], [[Resolution|resolution]] 1.56Å' scene=''> | + | <StructureSection load='6foh' size='340' side='right'caption='[[6foh]], [[Resolution|resolution]] 1.56Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6foh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FOH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6foh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FOH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FOH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.56Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FAHD1, C16orf36, YISKL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6foh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6foh OCA], [http://pdbe.org/6foh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6foh RCSB], [http://www.ebi.ac.uk/pdbsum/6foh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6foh ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6foh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6foh OCA], [https://pdbe.org/6foh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6foh RCSB], [https://www.ebi.ac.uk/pdbsum/6foh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6foh ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FAHD1_HUMAN FAHD1_HUMAN]] Probable mitochondrial acylpyruvase which is able to hydrolyze acetylpyruvate and fumarylpyruvate in vitro.<ref>PMID:15551868</ref> | + | [https://www.uniprot.org/uniprot/FAHD1_HUMAN FAHD1_HUMAN] Probable mitochondrial acylpyruvase which is able to hydrolyze acetylpyruvate and fumarylpyruvate in vitro.<ref>PMID:15551868</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Naschberger, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Weiss, A K.H]] | + | [[Category: Naschberger A]] |
| - | [[Category: Fahd 1]] | + | [[Category: Weiss AKH]] |
| - | [[Category: Fumarylacetoacetate hydrolase domain containing protein 1]]
| + | |
| - | [[Category: Hydrolase-lyase complex]]
| + | |
| - | [[Category: Hydrolase/lyase]]
| + | |
| Structural highlights
Function
FAHD1_HUMAN Probable mitochondrial acylpyruvase which is able to hydrolyze acetylpyruvate and fumarylpyruvate in vitro.[1]
Publication Abstract from PubMed
Whereas enzymes in the fumarylacetoacetate hydrolase (FAH) superfamily catalyze several distinct chemical reactions, the structural basis for their multi-functionality remains elusive. As a well-studied example, human FAH domain containing protein 1 (FAHD1) is a mitochondrial protein displaying both acylpyruvate hydrolase (ApH), and oxaloacetate decarboxylase (ODx) activity. As mitochondrial ODx, FAHD1 acts antagonistically to pyruvate carboxylase, a key metabolic enzyme. Despite its importance for mitochondrial function, very little is known about the catalytic mechanisms underlying FAHD1 enzymatic activities, and the architecture of its ligated active site is currently ill defined. We present crystallographic data of human FAHD1 that provide new insight into the structure of the catalytic center at high resolution, featuring a flexible 'lid'-like helical region which folds into a helical structure upon binding of the ODx inhibitor oxalate. The oxalate-driven structural transition results in the generation of a potential catalytic triad consisting of E33, H30 and an associated water molecule. In silico docking studies indicate that the substrate is further stabilized by a complex hydrogen bond network, involving amino acids Q109 and K123, identified herein as potential key residues for FAHD1 catalytic activity. Mutation of amino acids H30, E33, and K123 each had discernible influence on the ApH and/or ODx activity of FAHD1, suggesting distinct catalytic mechanisms for both activities. The structural analysis presented here provides a defined structural map of the active site of FAHD1, and contributes to a better understanding of the FAH superfamily of enzymes.
Structural basis for the bi-functionality of human oxaloacetate decarboxylase FAHD1.,Weiss AKH, Naschberger A, Loeffler JR, Gstach H, Bowler MW, Holzknecht M, Cappuccio E, Pittl A, Etemad S, Dunzendorfer-Matt T, Scheffzek K, Liedl KR, Jansen-Durr P Biochem J. 2018 Oct 22. pii: BCJ20180750. doi: 10.1042/BCJ20180750. PMID:30348641[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Manjasetty BA, Niesen FH, Delbruck H, Gotz F, Sievert V, Bussow K, Behlke J, Heinemann U. X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880. Biol Chem. 2004 Oct;385(10):935-42. PMID:15551868
- ↑ Weiss AKH, Naschberger A, Loeffler JR, Gstach H, Bowler MW, Holzknecht M, Cappuccio E, Pittl A, Etemad S, Dunzendorfer-Matt T, Scheffzek K, Liedl KR, Jansen-Durr P. Structural basis for the bi-functionality of human oxaloacetate decarboxylase FAHD1. Biochem J. 2018 Oct 22. pii: BCJ20180750. doi: 10.1042/BCJ20180750. PMID:30348641 doi:http://dx.doi.org/10.1042/BCJ20180750
|
