1ege: Difference between revisions
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==Overview== | ==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 ... | 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. | ||
==About this Structure== | ==About this Structure== | ||
1EGE is a | 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] Structure known Active Sites: CA1, CA2, CA3 and CA4. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EGE OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: flavoprotein]] | [[Category: flavoprotein]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:09:01 2007'' | ||
