3b96

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Revision as of 07:58, 25 October 2017

Structural Basis for Substrate Fatty-Acyl Chain Specificity: Crystal Structure of Human Very-Long-Chain Acyl-CoA Dehydrogenase

Structural highlights

3b96 is a 1 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:	ACADVL, VLCAD (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ACADV_HUMAN] Defects in ACADVL are the cause of acyl-CoA dehydrogenase very long chain deficiency (ACADVLD) [MIM:201475]. ACADVLD is an autosomal recessive disease which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting.^[1] ^[2] ^[3]

Function

[ACADV_HUMAN] Active toward esters of long-chain and very long chain fatty acids such as palmitoyl-CoA, mysritoyl-CoA and stearoyl-CoA. Can accommodate substrate acyl chain lengths as long as 24 carbons, but shows little activity for substrates of less than 12 carbons.^[4]

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

Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a member of the family of acyl-CoA dehydrogenases (ACADs). Unlike the other ACADs, which are soluble homotetramers, VLCAD is a homodimer associated with the mitochondrial membrane. VLCAD also possesses an additional 180 residues in the C terminus that are not present in the other ACADs. We have determined the crystal structure of VLCAD complexed with myristoyl-CoA, obtained by co-crystallization, to 1.91-A resolution. The overall fold of the N-terminal approximately 400 residues of VLCAD is similar to that of the soluble ACADs including medium-chain acyl-CoA dehydrogenase (MCAD). The novel C-terminal domain forms an alpha-helical bundle that is positioned perpendicular to the two N-terminal helical domains. The fatty acyl moiety of the bound substrate/product is deeply imbedded inside the protein; however, the adenosine pyrophosphate portion of the C14-CoA ligand is disordered because of partial hydrolysis of the thioester bond and high mobility of the CoA moiety. The location of Glu-422 with respect to the C2-C3 of the bound ligand and FAD confirms Glu-422 to be the catalytic base. In MCAD, Gln-95 and Glu-99 form the base of the substrate binding cavity. In VLCAD, these residues are glycines (Gly-175 and Gly-178), allowing the binding channel to extend for an additional 12A and permitting substrate acyl chain lengths as long as 24 carbons to bind. VLCAD deficiency is among the more common defects of mitochondrial beta-oxidation and, if left undiagnosed, can be fatal. This structure allows us to gain insight into how a variant VLCAD genotype results in a clinical phenotype.

Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase.,McAndrew RP, Wang Y, Mohsen AW, He M, Vockley J, Kim JJ J Biol Chem. 2008 Apr 4;283(14):9435-43. Epub 2008 Jan 28. PMID:18227065^[5]

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

References

↑ Souri M, Aoyama T, Orii K, Yamaguchi S, Hashimoto T. Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients. Am J Hum Genet. 1996 Jan;58(1):97-106. PMID:8554073
↑ Smelt AH, Poorthuis BJ, Onkenhout W, Scholte HR, Andresen BS, van Duinen SG, Gregersen N, Wintzen AR. Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset. Ann Neurol. 1998 Apr;43(4):540-4. PMID:9546340 doi:10.1002/ana.410430422
↑ Mathur A, Sims HF, Gopalakrishnan D, Gibson B, Rinaldo P, Vockley J, Hug G, Strauss AW. Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death. Circulation. 1999 Mar 16;99(10):1337-43. PMID:10077518
↑ McAndrew RP, Wang Y, Mohsen AW, He M, Vockley J, Kim JJ. Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase. J Biol Chem. 2008 Apr 4;283(14):9435-43. Epub 2008 Jan 28. PMID:18227065 doi:10.1074/jbc.M709135200
↑ McAndrew RP, Wang Y, Mohsen AW, He M, Vockley J, Kim JJ. Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase. J Biol Chem. 2008 Apr 4;283(14):9435-43. Epub 2008 Jan 28. PMID:18227065 doi:10.1074/jbc.M709135200

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3b96"

@@ Line 1: / Line 1: @@
 ==Structural Basis for Substrate Fatty-Acyl Chain Specificity: Crystal Structure of Human Very-Long-Chain Acyl-CoA Dehydrogenase==
 <StructureSection load='3b96' size='340' side='right' caption='[[3b96]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACADVL, VLCAD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3b96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b96 OCA], [http://pdbe.org/3b96 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3b96 RCSB], [http://www.ebi.ac.uk/pdbsum/3b96 PDBsum]</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=3b96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b96 OCA], [http://pdbe.org/3b96 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3b96 RCSB], [http://www.ebi.ac.uk/pdbsum/3b96 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3b96 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 3b96" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Acyl-CoA dehydrogenase|Acyl-CoA dehydrogenase]]
 == References ==
 <references/>
@@ Line 44: / Line 42: @@
 [[Category: Vockley, J]]
 [[Category: Wang, Y]]
+[[Category: Acetylation]]
 [[Category: Acyl-coa]]
+[[Category: Alternative splicing]]
 [[Category: Cardiomyopathy]]
 [[Category: Dehydrogenase]]
@@ Line 57: / Line 57: @@
 [[Category: Mitochondrion]]
 [[Category: Oxidoreductase]]
+[[Category: Polymorphism]]
 [[Category: Transit peptide]]
+[[Category: Ubl conjugation]]
 [[Category: Very long chain]]

3b96

From Proteopedia

Revision as of 07:58, 25 October 2017

Structural Basis for Substrate Fatty-Acyl Chain Specificity: Crystal Structure of Human Very-Long-Chain Acyl-CoA Dehydrogenase

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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