From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1ege.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:1ege.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1ege| PDB=1ege | SCENE= }} | | {{STRUCTURE_1ege| PDB=1ege | SCENE= }} |
| | | | |
| - | '''STRUCTURE OF T255E, E376G MUTANT OF HUMAN MEDIUM CHAIN ACYL-COA DEHYDROGENASE'''
| + | ===STRUCTURE OF T255E, E376G MUTANT OF HUMAN MEDIUM CHAIN ACYL-COA DEHYDROGENASE=== |
| | | | |
| | | | |
| - | ==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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8823176}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8823176 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_8823176}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 32: |
Line 36: |
| | [[Category: Electron transfer]] | | [[Category: Electron transfer]] |
| | [[Category: Flavoprotein]] | | [[Category: Flavoprotein]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:04:09 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 00:39:24 2008'' |
Revision as of 21:39, 30 June 2008
Template:STRUCTURE 1ege
STRUCTURE OF T255E, E376G MUTANT OF HUMAN MEDIUM CHAIN ACYL-COA DEHYDROGENASE
Template:ABSTRACT PUBMED 8823176
About this Structure
1EGE is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Tue Jul 1 00:39:24 2008
