1il0
From Proteopedia
(New page: 200px<br /> <applet load="1il0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1il0, resolution 2.20Å" /> '''X-RAY CRYSTAL STRUC...) |
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caption="1il0, resolution 2.20Å" /> | caption="1il0, resolution 2.20Å" /> | ||
'''X-RAY CRYSTAL STRUCTURE OF THE E170Q MUTANT OF HUMAN L-3-HYDROXYACYL-COA DEHYDROGENASE'''<br /> | '''X-RAY CRYSTAL STRUCTURE OF THE E170Q MUTANT OF HUMAN L-3-HYDROXYACYL-COA DEHYDROGENASE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IL0 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 CAA and NAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-hydroxyacyl-CoA_dehydrogenase 3-hydroxyacyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.35 1.1.1.35] Full crystallographic information is available from [http:// | + | 1IL0 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=CAA:'>CAA</scene> and <scene name='pdbligand=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-hydroxyacyl-CoA_dehydrogenase 3-hydroxyacyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.35 1.1.1.35] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IL0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: abortive ternary complex]] | [[Category: abortive ternary complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:02:14 2008'' |
Revision as of 14:02, 15 February 2008
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X-RAY CRYSTAL STRUCTURE OF THE E170Q MUTANT OF HUMAN L-3-HYDROXYACYL-COA DEHYDROGENASE
Contents |
Overview
l-3-Hydroxyacyl-CoA dehydrogenase (HAD), the penultimate enzyme in the, beta-oxidation spiral, reversibly catalyzes the conversion of, l-3-hydroxyacyl-CoA to the corresponding 3-ketoacyl-CoA. Similar to other, dehydrogenases, HAD contains a general acid/base, His(158), which is, within hydrogen bond distance of a carboxylate, Glu(170). To investigate, its function in this catalytic dyad, Glu(170) was replaced with glutamine, (E170Q), and the mutant enzyme was characterized. Whereas substrate and, cofactor binding were unaffected by the mutation, E170Q exhibited, diminished catalytic activity. Protonation of the catalytic histidine did, not restore wild-type activity, indicating that modulation of the pK(a) of, His(158) is not the sole function of Glu(170). The pH profile of charge, transfer complex formation, an independent indicator of active site, integrity, was unaltered by the amino acid substitution, but the intensity, of the charge transfer band was diminished. This observation, coupled with, significantly reduced enzymatic stability of the E170Q mutant, implicates, Glu(170) in maintenance of active site architecture. Examination of the, crystal structure of E170Q in complex with NAD(+) and acetoacetyl-CoA (R =, 21.9%, R(free) = 27.6%, 2.2 A) reveals that Gln(170) no longer hydrogen, bonds to the side chain of His(158). Instead, the imidazole ring is nearly, perpendicular to its placement in the comparable native complex and no, longer positioned for efficient catalysis.
Disease
Known diseases associated with this structure: 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency OMIM:[300256], 3-hydroxyacyl-CoA dehydrogenase deficiency OMIM:[601609], Hyperinsulinemic hypoglycemia, familial, 4 OMIM:[601609]
About this Structure
1IL0 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as 3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35 Full crystallographic information is available from OCA.
Reference
Glutamate 170 of human l-3-hydroxyacyl-CoA dehydrogenase is required for proper orientation of the catalytic histidine and structural integrity of the enzyme., Barycki JJ, O'Brien LK, Strauss AW, Banaszak LJ, J Biol Chem. 2001 Sep 28;276(39):36718-26. Epub 2001 Jul 12. PMID:11451959
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