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| | <StructureSection load='1qcn' size='340' side='right'caption='[[1qcn]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1qcn' size='340' side='right'caption='[[1qcn]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1qcn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QCN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1qcn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QCN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
| + | |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1qco|1qco]], [[1qqj|1qqj]]</div></td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Fumarylacetoacetase Fumarylacetoacetase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.7.1.2 3.7.1.2] </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=1qcn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcn OCA], [https://pdbe.org/1qcn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qcn RCSB], [https://www.ebi.ac.uk/pdbsum/1qcn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qcn 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=1qcn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qcn OCA], [https://pdbe.org/1qcn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qcn RCSB], [https://www.ebi.ac.uk/pdbsum/1qcn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qcn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/FAAA_MOUSE FAAA_MOUSE] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Fumarylacetoacetase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Bhanumoorthy, P]] | + | [[Category: Bhanumoorthy P]] |
| - | [[Category: Bunick, G J]] | + | [[Category: Bunick GJ]] |
| - | [[Category: Harp, J M]] | + | [[Category: Harp JM]] |
| - | [[Category: Mueller, H A]] | + | [[Category: Mueller HA]] |
| - | [[Category: Timm, D E]] | + | [[Category: Timm DE]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Mixed beta sandwich roll]]
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| Structural highlights
Function
FAAA_MOUSE
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: Fumarylacetoacetate hydrolase (FAH) catalyzes the final step of tyrosine and phenylalanine catabolism, the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate, to yield fumarate and acetoacetate. FAH has no known sequence homologs and functions by an unknown mechanism. Carbon-carbon hydrolysis reactions are essential for the human metabolism of aromatic amino acids. FAH deficiency causes the fatal metabolic disease hereditary tyrosinemia type I. Carbon-carbon bond hydrolysis is also important in the microbial metabolism of aromatic compounds as part of the global carbon cycle. RESULTS: The FAH crystal structure has been determined by rapid, automated analysis of multiwavelength anomalous diffraction data. The FAH polypeptide folds into a 120-residue N-terminal domain and a 300-residue C-terminal domain. The C-terminal domain defines an unusual beta-strand topology and a novel 'mixed beta-sandwich roll' structure. The structure of FAH complexed with its physiological products was also determined. This structure reveals fumarate binding near the entrance to the active site and acetoacetate binding to an octahedrally coordinated calcium ion located in close proximity to a Glu-His dyad. CONCLUSIONS: FAH represents the first structure of a hydrolase that acts specifically on carbon-carbon bonds. FAH also defines a new class of metalloenzymes characterized by a unique alpha/beta fold. A mechanism involving a Glu-His-water catalytic triad is suggested based on structural observations, sequence conservation and mutational analysis. The histidine imidazole group is proposed to function as a general base. The Ca(2+) is proposed to function in binding substrate, activating the nucleophile and stabilizing a carbanion leaving group. An oxyanion hole formed from sidechains is proposed to stabilize a tetrahedral alkoxide transition state. The proton transferred to the carbanion leaving group is proposed to originate from a lysine sidechain. The results also reveal the molecular basis for mutations causing the hereditary tyrosinemia type 1.
Crystal structure and mechanism of a carbon-carbon bond hydrolase.,Timm DE, Mueller HA, Bhanumoorthy P, Harp JM, Bunick GJ Structure. 1999 Sep 15;7(9):1023-33. PMID:10508789[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Timm DE, Mueller HA, Bhanumoorthy P, Harp JM, Bunick GJ. Crystal structure and mechanism of a carbon-carbon bond hydrolase. Structure. 1999 Sep 15;7(9):1023-33. PMID:10508789
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