1il0
From Proteopedia
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| - | [[Image:1il0.jpg|left|200px]] | + | [[Image:1il0.jpg|left|200px]] |
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| - | '''X-RAY CRYSTAL STRUCTURE OF THE E170Q MUTANT OF HUMAN L-3-HYDROXYACYL-COA DEHYDROGENASE''' | + | {{Structure |
| + | |PDB= 1il0 |SIZE=350|CAPTION= <scene name='initialview01'>1il0</scene>, resolution 2.20Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CAA:ACETOACETYL-COENZYME+A'>CAA</scene> and <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= HCDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''X-RAY CRYSTAL STRUCTURE OF THE E170Q MUTANT OF HUMAN L-3-HYDROXYACYL-COA DEHYDROGENASE''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IL0 is a [ | + | 1IL0 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IL0 OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11451959 11451959] |
[[Category: 3-hydroxyacyl-CoA dehydrogenase]] | [[Category: 3-hydroxyacyl-CoA dehydrogenase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: abortive ternary complex]] | [[Category: abortive ternary complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:51:48 2008'' |
Revision as of 09:51, 20 March 2008
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| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | HCDH (Homo sapiens) | ||||||
| Activity: | 3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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