1u7t

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[[Image:1u7t.gif|left|200px]]
 
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==Crystal Structure of ABAD/HSD10 with a Bound Inhibitor==
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The line below this paragraph, containing "STRUCTURE_1u7t", creates the "Structure Box" on the page.
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<StructureSection load='1u7t' size='340' side='right'caption='[[1u7t]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1u7t]] is a 4 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=1U7T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U7T FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=TDT:1-AZEPAN-1-YL-2-PHENYL-2-(4-THIOXO-1,4-DIHYDRO-PYRAZOLO[3,4-D]PYRIMIDIN-5-YL)ETHANONE+ADDUCT'>TDT</scene></td></tr>
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{{STRUCTURE_1u7t| PDB=1u7t | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1u7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u7t OCA], [https://pdbe.org/1u7t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u7t RCSB], [https://www.ebi.ac.uk/pdbsum/1u7t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u7t ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/HCD2_HUMAN HCD2_HUMAN] Defects in HSD17B10 are the cause of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (MHBD deficiency) [MIM:[https://omim.org/entry/300438 300438]. MHBD deficiency leads to neurological abnormalities, including psychomotor retardation, and, in virtually all patients, loss of mental and motor skills. Defects in HSD17B10 are the cause of mental retardation syndromic X-linked type 10 (MRXS10) [MIM:[https://omim.org/entry/300220 300220]. MRXS10 is characterized by mild mental retardation, choreoathetosis and abnormal behavior.<ref>PMID:17236142</ref> A chromosomal microduplication involving HSD17B10 and HUWE1 is the cause of mental retardation X-linked type 17 (MRX17) [MIM:[https://omim.org/entry/300705 300705]; also known as mental retardation X-linked type 31 (MRX31). Mental retardation is characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. In contrast to syndromic or specific X-linked mental retardation which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation.<ref>PMID:18252223</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/HCD2_HUMAN HCD2_HUMAN] Functions in mitochondrial tRNA maturation. Part of mitochondrial ribonuclease P, an enzyme composed of MRPP1/TRMT10C, MRPP2/HSD17B10 and MRPP3/KIAA0391, which cleaves tRNA molecules in their 5'-ends. By interacting with intracellular amyloid-beta, it may contribute to the neuronal dysfunction associated with Alzheimer disease (AD).<ref>PMID:18984158</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u7/1u7t_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1u7t ConSurf].
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<div style="clear:both"></div>
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'''Crystal Structure of ABAD/HSD10 with a Bound Inhibitor'''
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==See Also==
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*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]]
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== References ==
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==Overview==
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<references/>
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The enzyme 17beta-hydroxysteroid dehydrogenase type 10 (HSD10), also known as amyloid beta-peptide-binding alcohol dehydrogenase (ABAD), has been implicated in the development of Alzheimer's disease. This protein, a member of the short-chain dehydrogenase/reductase family of enzymes, has been shown to bind beta-amyloid and to participate in beta-amyloid neurotoxicity. We have determined the crystal structure of human ABAD/HSD10 complexed with NAD(+) and an inhibitory small molecule. The inhibitor occupies the substrate-binding site and forms a covalent adduct with the NAD(+) cofactor. The crystal structure provides a basis for the design of potent, highly specific ABAD/HSD10 inhibitors with potential application in the treatment of Alzheimer's disease.
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__TOC__
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</StructureSection>
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==About this Structure==
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1U7T is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U7T OCA].
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==Reference==
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Crystal structure of human ABAD/HSD10 with a bound inhibitor: implications for design of Alzheimer's disease therapeutics., Kissinger CR, Rejto PA, Pelletier LA, Thomson JA, Showalter RE, Abreo MA, Agree CS, Margosiak S, Meng JJ, Aust RM, Vanderpool D, Li B, Tempczyk-Russell A, Villafranca JE, J Mol Biol. 2004 Sep 17;342(3):943-52. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15342248 15342248]
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[[Category: 3-hydroxyacyl-CoA dehydrogenase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Kissinger, C R.]]
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[[Category: Kissinger CR]]
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[[Category: Pelletier, L A.]]
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[[Category: Pelletier LA]]
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[[Category: Rejto, P A.]]
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[[Category: Rejto PA]]
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[[Category: Showalter, R E.]]
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[[Category: Showalter RE]]
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[[Category: Villafranca, J E.]]
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[[Category: Villafranca JE]]
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[[Category: Protein-inhibitor complex]]
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[[Category: Rossmann fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:52:00 2008''
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Current revision

Crystal Structure of ABAD/HSD10 with a Bound Inhibitor

PDB ID 1u7t

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