1s5o: Difference between revisions
New page: left|200px<br /> <applet load="1s5o" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s5o, resolution 1.8Å" /> '''Structural and Mutat... |
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[[Image:1s5o.gif|left|200px]]<br /> | [[Image:1s5o.gif|left|200px]]<br /><applet load="1s5o" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1s5o, resolution 1.8Å" /> | caption="1s5o, resolution 1.8Å" /> | ||
'''Structural and Mutational Characterization of L-carnitine Binding to Human carnitine Acetyltransferase'''<br /> | '''Structural and Mutational Characterization of L-carnitine Binding to Human carnitine Acetyltransferase'''<br /> | ||
==Overview== | ==Overview== | ||
We report the crystal structure of a binary complex of human peroxisomal | We report the crystal structure of a binary complex of human peroxisomal carnitine acetyltransferase and the substrate l-carnitine, refined to a resolution of 1.8 Angstrom with an R(factor) value of 18.9% (R(free)=22.3%). L-carnitine binds to a preformed pocket in the active site tunnel of carnitine acetyltransferase aligned with His(322). The quaternary nitrogen of carnitine forms a pi-cation interaction with Phe(545), while Arg(497) forms an electrostatic interaction with the negatively charged carboxylate group. An extensive hydrogen bond network also occurs between the carboxylate group and Tyr(431), Thr(444), and a bound water molecule. Site-directed mutagenesis and kinetic characterization reveals that Tyr(431), Thr(444), Arg(497), and Phe(545) are essential for high affinity binding of L-carnitine. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1S5O 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 152 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Carnitine_O-acetyltransferase Carnitine O-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.7 2.3.1.7] Full crystallographic information is available from [http:// | 1S5O 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=152:'>152</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Carnitine_O-acetyltransferase Carnitine O-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.7 2.3.1.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S5O OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: x-ray structure]] | [[Category: x-ray structure]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:58:12 2008'' | ||
Revision as of 15:58, 21 February 2008
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Structural and Mutational Characterization of L-carnitine Binding to Human carnitine Acetyltransferase
OverviewOverview
We report the crystal structure of a binary complex of human peroxisomal carnitine acetyltransferase and the substrate l-carnitine, refined to a resolution of 1.8 Angstrom with an R(factor) value of 18.9% (R(free)=22.3%). L-carnitine binds to a preformed pocket in the active site tunnel of carnitine acetyltransferase aligned with His(322). The quaternary nitrogen of carnitine forms a pi-cation interaction with Phe(545), while Arg(497) forms an electrostatic interaction with the negatively charged carboxylate group. An extensive hydrogen bond network also occurs between the carboxylate group and Tyr(431), Thr(444), and a bound water molecule. Site-directed mutagenesis and kinetic characterization reveals that Tyr(431), Thr(444), Arg(497), and Phe(545) are essential for high affinity binding of L-carnitine.
DiseaseDisease
Known disease associated with this structure: Carnitine acetyltransferase deficiency (1) OMIM:[600184]
About this StructureAbout this Structure
1S5O is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Carnitine O-acetyltransferase, with EC number 2.3.1.7 Full crystallographic information is available from OCA.
ReferenceReference
Structural and mutational characterization of L-carnitine binding to human carnitine acetyltransferase., Govindasamy L, Kukar T, Lian W, Pedersen B, Gu Y, Agbandje-McKenna M, Jin S, McKenna R, Wu D, J Struct Biol. 2004 Jun;146(3):416-24. PMID:15099582
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