4dcp: Difference between revisions
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[[ | ==Crystal Structure of caspase 3, L168F mutant== | ||
<StructureSection load='4dcp' size='340' side='right' caption='[[4dcp]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4dcp]] is a 6 chain structure with 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=4DCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DCP FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ASJ:(3S)-3-AMINO-4-HYDROXYBUTANOIC+ACID'>ASJ</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dcj|4dcj]], [[4dco|4dco]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-3 Caspase-3], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.56 3.4.22.56] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dcp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dcp RCSB], [http://www.ebi.ac.uk/pdbsum/4dcp PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Various apoptotic signals can activate caspases 3 and 7 by triggering the L2 loop cleavage of their proenzymes. These two enzymes have highly similar structures and functions, and serve as apoptotic executioners. The structures of caspase 7 and procaspase 7 differ significantly in the conformation of the loops constituting the active site, indicating that the enzyme undergoes a large structural change during activation. To define the role of the leucine residue on the L2 loop, which shows the largest movement during enzyme activation but has not yet been studied, Leu168 of caspase 3 and Leu191 of caspase 7 were mutated. Kinetic analysis indicated that the mutation of the leucine residues sometimes improved the Km but also greatly decreased the kcat, resulting in an overall decrease in enzyme activity. The tryptophan fluorescence change at excitation/emission = 280/350 nm upon L2-L2' loop cleavage was found to be higher in catalytically active mutants, including the corresponding wild-type caspase, than in the inactive mutants. The crystal structures of the caspase 3 mutants were solved and compared with that of wild-type. Significant alterations in the conformations of the L1 and L4 loops were found. These results indicate that the leucine residue on the L2 loop has an important role in maintaining the catalytic activity of caspases 3 and 7. | |||
Molecular insight into the role of the leucine residue on the L2 loop in the catalytic activity of caspases 3 and 7.,Kang HJ, Lee YM, Jeong MS, Kim M, Bae KH, Kim SJ, Chung SJ Biosci Rep. 2012 Jun;32(3):305-13. PMID:22304005<ref>PMID:22304005</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[Caspase|Caspase]] | |||
== | == References == | ||
[[ | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Caspase-3]] | [[Category: Caspase-3]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Chung, S J | [[Category: Chung, S J]] | ||
[[Category: Kang, H J | [[Category: Kang, H J]] | ||
[[Category: Kim, S J | [[Category: Kim, S J]] | ||
[[Category: Alpha/beta hydrolase]] | [[Category: Alpha/beta hydrolase]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 17:49, 9 December 2014
Crystal Structure of caspase 3, L168F mutantCrystal Structure of caspase 3, L168F mutant
Structural highlights
Publication Abstract from PubMedVarious apoptotic signals can activate caspases 3 and 7 by triggering the L2 loop cleavage of their proenzymes. These two enzymes have highly similar structures and functions, and serve as apoptotic executioners. The structures of caspase 7 and procaspase 7 differ significantly in the conformation of the loops constituting the active site, indicating that the enzyme undergoes a large structural change during activation. To define the role of the leucine residue on the L2 loop, which shows the largest movement during enzyme activation but has not yet been studied, Leu168 of caspase 3 and Leu191 of caspase 7 were mutated. Kinetic analysis indicated that the mutation of the leucine residues sometimes improved the Km but also greatly decreased the kcat, resulting in an overall decrease in enzyme activity. The tryptophan fluorescence change at excitation/emission = 280/350 nm upon L2-L2' loop cleavage was found to be higher in catalytically active mutants, including the corresponding wild-type caspase, than in the inactive mutants. The crystal structures of the caspase 3 mutants were solved and compared with that of wild-type. Significant alterations in the conformations of the L1 and L4 loops were found. These results indicate that the leucine residue on the L2 loop has an important role in maintaining the catalytic activity of caspases 3 and 7. Molecular insight into the role of the leucine residue on the L2 loop in the catalytic activity of caspases 3 and 7.,Kang HJ, Lee YM, Jeong MS, Kim M, Bae KH, Kim SJ, Chung SJ Biosci Rep. 2012 Jun;32(3):305-13. PMID:22304005[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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