1ege
From Proteopedia
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==STRUCTURE OF T255E, E376G MUTANT OF HUMAN MEDIUM CHAIN ACYL-COA DEHYDROGENASE== | ==STRUCTURE OF T255E, E376G MUTANT OF HUMAN MEDIUM CHAIN ACYL-COA DEHYDROGENASE== | ||
| - | <StructureSection load='1ege' size='340' side='right' caption='[[1ege]], [[Resolution|resolution]] 2.75Å' scene=''> | + | <StructureSection load='1ege' size='340' side='right'caption='[[1ege]], [[Resolution|resolution]] 2.75Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1ege]] is a 4 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1ege]] 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=1EGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EGE FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ege FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ege OCA], [https://pdbe.org/1ege PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ege RCSB], [https://www.ebi.ac.uk/pdbsum/1ege PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ege ProSAT]</span></td></tr> |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/ACADM_HUMAN ACADM_HUMAN] Defects in ACADM are the cause of acyl-CoA dehydrogenase medium-chain deficiency (ACADMD) [MIM:[https://omim.org/entry/201450 201450]. It is an autosomal recessive disease which causes fasting hypoglycemia, hepatic dysfunction, and encephalopathy, often resulting in death in infancy.<ref>PMID:2393404</ref> <ref>PMID:2394825</ref> <ref>PMID:2251268</ref> <ref>PMID:1684086</ref> <ref>PMID:1902818</ref> <ref>PMID:1671131</ref> <ref>PMID:8198141</ref> <ref>PMID:7603790</ref> <ref>PMID:7929823</ref> <ref>PMID:9158144</ref> <ref>PMID:9882619</ref> <ref>PMID:10767181</ref> <ref>PMID:11349232</ref> <ref>PMID:11409868</ref> <ref>PMID:11486912</ref> |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/ACADM_HUMAN ACADM_HUMAN] This enzyme is specific for acyl chain lengths of 4 to 16. |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/1ege_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/1ege_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
| - | </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/ | + | </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=1ege ConSurf]. |
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Crystal structures of the wild type human medium-chain acyl-CoA dehydrogenase (MCADH) and a double mutant in which its active center base-arrangement has been altered to that of long chain acyl-CoA dehydrogenase (LCADH), Glu376Gly/Thr255Glu, have been determined by X-ray crystallography at 2.75 and 2.4 A resolution, respectively. The catalytic base responsible for the alpha-proton abstraction from the thioester substrate is Glu376 in MCADH, while that in LCADH is Glu255 (MCADH numbering), located over 100 residues away in its primary amino acid sequence. The structures of the mutant complexed with C8-, C12, and C14-CoA have also been determined. The human enzyme structure is essentially the same as that of the pig enzyme. The structure of the mutant is unchanged upon ligand binding except for the conformations of a few side chains in the active site cavity. The substrate with chain length longer than C12 binds to the enzyme in multiple conformations at its omega-end. Glu255 has two conformations, "active" and "resting" forms, with the latter apparently stabilized by forming a hydrogen bond with Glu99. Both the direction in which Glu255 approaches the C alpha atom of the substrate and the distance between the Glu255 carboxylate and the C alpha atom are different from those of Glu376; these factors are responsible for the intrinsic differences in the kinetic properties as well as the substrate specificity. Solvent accessible space at the "midsection" of the active site cavity, where the C alpha-C beta bond of the thioester substrate and the isoalloxazine ring of the FAD are located, is larger in the mutant than in the wild type enzyme, implying greater O2 accessibility in the mutant which might account for the higher oxygen reactivity. | ||
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| - | Crystal structures of the wild type and the Glu376Gly/Thr255Glu mutant of human medium-chain acyl-CoA dehydrogenase: influence of the location of the catalytic base on substrate specificity.,Lee HJ, Wang M, Paschke R, Nandy A, Ghisla S, Kim JJ Biochemistry. 1996 Sep 24;35(38):12412-20. PMID:8823176<ref>PMID:8823176</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
==See Also== | ==See Also== | ||
| - | *[[Acyl-CoA dehydrogenase|Acyl-CoA dehydrogenase]] | + | *[[Acyl-CoA dehydrogenase 3D structures|Acyl-CoA dehydrogenase 3D structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Ghisla | + | [[Category: Ghisla S]] |
| - | [[Category: Kim | + | [[Category: Kim JP]] |
| - | [[Category: Lee | + | [[Category: Lee HJ]] |
| - | [[Category: Nandy | + | [[Category: Nandy A]] |
| - | [[Category: Paschke | + | [[Category: Paschke R]] |
| - | [[Category: Wang | + | [[Category: Wang M]] |
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Current revision
STRUCTURE OF T255E, E376G MUTANT OF HUMAN MEDIUM CHAIN ACYL-COA DEHYDROGENASE
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Categories: Homo sapiens | Large Structures | Ghisla S | Kim JP | Lee HJ | Nandy A | Paschke R | Wang M
