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1u7t

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Revision as of 07:24, 30 December 2020

Crystal Structure of ABAD/HSD10 with a Bound Inhibitor

Structural highlights

1u7t is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	HADH2, ERAB, XH98G2, SCHAD (HUMAN)
Activity:	3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[HCD2_HUMAN] Defects in HSD17B10 are the cause of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (MHBD deficiency) [MIM: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:300220]. MRXS10 is characterized by mild mental retardation, choreoathetosis and abnormal behavior.^[1] A chromosomal microduplication involving HSD17B10 and HUWE1 is the cause of mental retardation X-linked type 17 (MRX17) [MIM: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.^[2]

Function

[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).^[3]

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

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.

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:15342248^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lenski C, Kooy RF, Reyniers E, Loessner D, Wanders RJ, Winnepenninckx B, Hellebrand H, Engert S, Schwartz CE, Meindl A, Ramser J. The reduced expression of the HADH2 protein causes X-linked mental retardation, choreoathetosis, and abnormal behavior. Am J Hum Genet. 2007 Feb;80(2):372-7. Epub 2006 Dec 28. PMID:17236142 doi:10.1086/511527
↑ Froyen G, Corbett M, Vandewalle J, Jarvela I, Lawrence O, Meldrum C, Bauters M, Govaerts K, Vandeleur L, Van Esch H, Chelly J, Sanlaville D, van Bokhoven H, Ropers HH, Laumonnier F, Ranieri E, Schwartz CE, Abidi F, Tarpey PS, Futreal PA, Whibley A, Raymond FL, Stratton MR, Fryns JP, Scott R, Peippo M, Sipponen M, Partington M, Mowat D, Field M, Hackett A, Marynen P, Turner G, Gecz J. Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. Am J Hum Genet. 2008 Feb;82(2):432-43. Epub 2008 Jan 24. PMID:18252223 doi:S0002-9297(07)00036-5
↑ Holzmann J, Frank P, Loffler E, Bennett KL, Gerner C, Rossmanith W. RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell. 2008 Oct 31;135(3):462-74. PMID:18984158 doi:S0092-8674(08)01135-5
↑ 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. Crystal structure of human ABAD/HSD10 with a bound inhibitor: implications for design of Alzheimer's disease therapeutics. J Mol Biol. 2004 Sep 17;342(3):943-52. PMID:15342248 doi:10.1016/j.jmb.2004.07.071

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1u7t"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of ABAD/HSD10 with a Bound Inhibitor==
-<StructureSection load='1u7t' size='340' side='right' caption='[[1u7t]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='1u7t' size='340' side='right'caption='[[1u7t]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1u7t]] is a 4 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=1U7T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U7T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1u7t]] is a 4 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=1U7T OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1U7T FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
+</td></tr><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>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HADH2, ERAB, XH98G2, SCHAD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-hydroxyacyl-CoA_dehydrogenase 3-hydroxyacyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.35 1.1.1.35] </span></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=1u7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u7t OCA], [http://pdbe.org/1u7t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u7t RCSB], [http://www.ebi.ac.uk/pdbsum/1u7t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u7t ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1u7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u7t OCA], [http://pdbe.org/1u7t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u7t RCSB], [http://www.ebi.ac.uk/pdbsum/1u7t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u7t ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 34: / Line 34: @@
 ==See Also==
-*[[Alcohol dehydrogenase|Alcohol dehydrogenase]]
+*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]]
 == References ==
 <references/>
@@ Line 41: / Line 41: @@
 [[Category: 3-hydroxyacyl-CoA dehydrogenase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Kissinger, C R]]
 [[Category: Pelletier, L A]]

1u7t

From Proteopedia

Revision as of 07:24, 30 December 2020

Crystal Structure of ABAD/HSD10 with a Bound Inhibitor

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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