2h7c: Difference between revisions
New page: left|200px<br /> <applet load="2h7c" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h7c, resolution 2.00Å" /> '''Crystal structure o... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2h7c.gif|left|200px]]<br /> | [[Image:2h7c.gif|left|200px]]<br /><applet load="2h7c" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2h7c" size=" | |||
caption="2h7c, resolution 2.00Å" /> | caption="2h7c, resolution 2.00Å" /> | ||
'''Crystal structure of human carboxylesterase in complex with Coenzyme A'''<br /> | '''Crystal structure of human carboxylesterase in complex with Coenzyme A'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==Overview== | ||
Human carboxylesterase 1 (hCE1) is a drug and endobiotic-processing serine, hydrolase that exhibits relatively broad substrate specificity. It has, been implicated in a variety of endogenous cholesterol metabolism pathways, including the following apparently disparate reactions: cholesterol ester, hydrolysis (CEH), fatty acyl Coenzyme A hydrolysis (FACoAH), acyl-Coenzyme, A:cholesterol acyltransfer (ACAT), and fatty acyl ethyl ester synthesis, (FAEES). The structural basis for the ability of hCE1 to perform these, catalytic actions involving large substrates and products has remained, unclear. Here we present four crystal structures of the hCE1 glycoprotein, in complexes with the following endogenous substrates or substrate, analogues: Coenzyme A, the fatty acid palmitate, and the bile acids, cholate and taurocholate. While the active site of hCE1 was known to be, promiscuous and capable of interacting with a variety of chemically, distinct ligands, these structures reveal that the enzyme contains two, additional ligand-binding sites and that each site also exhibits, relatively non-specific ligand-binding properties. Using this multisite, promiscuity, hCE1 appears structurally capable of assembling several, catalytic events depending, apparently, on the physiological state of the, cellular environment. These results expand our understanding of enzyme, promiscuity and indicate that, in the case of hCE1, multiple non-specific, sites are employed to perform distinct catalytic actions. | Human carboxylesterase 1 (hCE1) is a drug and endobiotic-processing serine, hydrolase that exhibits relatively broad substrate specificity. It has, been implicated in a variety of endogenous cholesterol metabolism pathways, including the following apparently disparate reactions: cholesterol ester, hydrolysis (CEH), fatty acyl Coenzyme A hydrolysis (FACoAH), acyl-Coenzyme, A:cholesterol acyltransfer (ACAT), and fatty acyl ethyl ester synthesis, (FAEES). The structural basis for the ability of hCE1 to perform these, catalytic actions involving large substrates and products has remained, unclear. Here we present four crystal structures of the hCE1 glycoprotein, in complexes with the following endogenous substrates or substrate, analogues: Coenzyme A, the fatty acid palmitate, and the bile acids, cholate and taurocholate. While the active site of hCE1 was known to be, promiscuous and capable of interacting with a variety of chemically, distinct ligands, these structures reveal that the enzyme contains two, additional ligand-binding sites and that each site also exhibits, relatively non-specific ligand-binding properties. Using this multisite, promiscuity, hCE1 appears structurally capable of assembling several, catalytic events depending, apparently, on the physiological state of the, cellular environment. These results expand our understanding of enzyme, promiscuity and indicate that, in the case of hCE1, multiple non-specific, sites are employed to perform distinct catalytic actions. | ||
==About this Structure== | ==About this Structure== | ||
2H7C 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 NAG, NDG, SIA, SO4 and COA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxylesterase Carboxylesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.1 3.1.1.1] Full crystallographic information is available from [http:// | 2H7C 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=NAG:'>NAG</scene>, <scene name='pdbligand=NDG:'>NDG</scene>, <scene name='pdbligand=SIA:'>SIA</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=COA:'>COA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Carboxylesterase Carboxylesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.1 3.1.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H7C OCA]. | ||
==Reference== | ==Reference== | ||
| Line 34: | Line 30: | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:31:36 2008'' | ||
Revision as of 13:31, 23 January 2008
|
Crystal structure of human carboxylesterase in complex with Coenzyme A
OverviewOverview
Human carboxylesterase 1 (hCE1) is a drug and endobiotic-processing serine, hydrolase that exhibits relatively broad substrate specificity. It has, been implicated in a variety of endogenous cholesterol metabolism pathways, including the following apparently disparate reactions: cholesterol ester, hydrolysis (CEH), fatty acyl Coenzyme A hydrolysis (FACoAH), acyl-Coenzyme, A:cholesterol acyltransfer (ACAT), and fatty acyl ethyl ester synthesis, (FAEES). The structural basis for the ability of hCE1 to perform these, catalytic actions involving large substrates and products has remained, unclear. Here we present four crystal structures of the hCE1 glycoprotein, in complexes with the following endogenous substrates or substrate, analogues: Coenzyme A, the fatty acid palmitate, and the bile acids, cholate and taurocholate. While the active site of hCE1 was known to be, promiscuous and capable of interacting with a variety of chemically, distinct ligands, these structures reveal that the enzyme contains two, additional ligand-binding sites and that each site also exhibits, relatively non-specific ligand-binding properties. Using this multisite, promiscuity, hCE1 appears structurally capable of assembling several, catalytic events depending, apparently, on the physiological state of the, cellular environment. These results expand our understanding of enzyme, promiscuity and indicate that, in the case of hCE1, multiple non-specific, sites are employed to perform distinct catalytic actions.
About this StructureAbout this Structure
2H7C is a Single protein structure of sequence from Homo sapiens with , , , and as ligands. Active as Carboxylesterase, with EC number 3.1.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1., Bencharit S, Edwards CC, Morton CL, Howard-Williams EL, Kuhn P, Potter PM, Redinbo MR, J Mol Biol. 2006 Oct 13;363(1):201-14. Epub 2006 Aug 15. PMID:16962139
Page seeded by OCA on Wed Jan 23 12:31:36 2008