1ege
From Proteopedia
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| - | [[Image:1ege.jpg|left|200px]]<br /><applet load="1ege" size=" | + | [[Image:1ege.jpg|left|200px]]<br /><applet load="1ege" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ege, resolution 2.75Å" /> | caption="1ege, resolution 2.75Å" /> | ||
'''STRUCTURE OF T255E, E376G MUTANT OF HUMAN MEDIUM CHAIN ACYL-COA DEHYDROGENASE'''<br /> | '''STRUCTURE OF T255E, E376G MUTANT OF HUMAN MEDIUM CHAIN ACYL-COA DEHYDROGENASE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1EGE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Acyl-CoA_dehydrogenase Acyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.3 1.3.99.3] Known structural/functional Sites: <scene name='pdbsite=CA1:Catalytic Base In Chain A'>CA1</scene>, <scene name='pdbsite=CA2:Catalytic Base In Chain B'>CA2</scene>, <scene name='pdbsite=CA3:Catalytic Base In Chain C'>CA3</scene> and <scene name='pdbsite=CA4:Catalytic Base In Chain D'>CA4</scene>. Full crystallographic information is available from [http:// | + | 1EGE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Acyl-CoA_dehydrogenase Acyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.3 1.3.99.3] Known structural/functional Sites: <scene name='pdbsite=CA1:Catalytic+Base+In+Chain+A'>CA1</scene>, <scene name='pdbsite=CA2:Catalytic+Base+In+Chain+B'>CA2</scene>, <scene name='pdbsite=CA3:Catalytic+Base+In+Chain+C'>CA3</scene> and <scene name='pdbsite=CA4:Catalytic+Base+In+Chain+D'>CA4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EGE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: flavoprotein]] | [[Category: flavoprotein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:39:11 2008'' |
Revision as of 07:39, 3 February 2008
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STRUCTURE OF T255E, E376G MUTANT OF HUMAN MEDIUM CHAIN ACYL-COA DEHYDROGENASE
Contents |
Overview
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.
Disease
Known disease associated with this structure: Acyl-CoA dehydrogenase, medium chain, deficiency of OMIM:[607008]
About this Structure
1EGE is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Acyl-CoA dehydrogenase, with EC number 1.3.99.3 Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.
Reference
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
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