4ov4: Difference between revisions
No edit summary |
No edit summary |
||
| Line 6: | Line 6: | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ov9|4ov9]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ov9|4ov9]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-isopropylmalate_synthase 2-isopropylmalate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.13 2.3.3.13] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-isopropylmalate_synthase 2-isopropylmalate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.13 2.3.3.13] </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=4ov4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ov4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ov4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ov4 PDBsum]</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=4ov4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ov4 OCA], [http://pdbe.org/4ov4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ov4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ov4 PDBsum]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The committed step of leucine biosynthesis, converting acetyl-CoA and alpha-ketoisovalerate into alpha-isopropylmalate, is catalyzed by alpha-isopropylmalate synthase (IPMS), an allosteric enzyme subjected to feedback inhibition by the end product L-leucine. We characterized the short form IPMS from Leptospira biflexa (LbIPMS2), which exhibits a catalytic activity comparable with that of the long form IPMS (LbIPMS1) and has a similar N-terminal domain followed by subdomain I and subdomain II but lacks the whole C-terminal regulatory domain. We found that partial deletion of the regulatory domain of LbIPMS1 resulted in a loss of about 50% of the catalytic activity; however, when the regulatory domain was deleted up to Arg-385, producing a protein that is almost equivalent to the intact LbIPMS2, about 90% of the activity was maintained. Moreover, in LbIPMS2 or LbIPMS1, further deletion of several residues from the C terminus of subdomain II significantly impaired or completely abolished the catalytic activity, respectively. These results define a complete and independently functional catalytic module of IPMS consisting of both the N-terminal domain and the two subdomains. Structural comparison of LbIPMS2 and the Mycobacterium tuberculosis IPMS revealed two different conformations of subdomain II that likely represent two substrate-binding states related to cooperative catalysis. The biochemical and structural analyses together with the previously published hydrogen-deuterium exchange data led us to propose a conformation transition mechanism for feedback inhibition mediated by subdomains I and II that might associated with alteration of the binding affinity toward acetyl-CoA. | |||
Subdomain II of alpha-isopropylmalate synthase is essential for activity: inferring a mechanism of feedback inhibition.,Zhang Z, Wu J, Lin W, Wang J, Yan H, Zhao W, Ma J, Ding J, Zhang P, Zhao GP J Biol Chem. 2014 Oct 3;289(40):27966-78. doi: 10.1074/jbc.M114.559716. Epub 2014, Aug 15. PMID:25128527<ref>PMID:25128527</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ov4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 21:32, 30 November 2015
Isopropylmalate synthase binding with ketoisovalerateIsopropylmalate synthase binding with ketoisovalerate
Structural highlights
Publication Abstract from PubMedThe committed step of leucine biosynthesis, converting acetyl-CoA and alpha-ketoisovalerate into alpha-isopropylmalate, is catalyzed by alpha-isopropylmalate synthase (IPMS), an allosteric enzyme subjected to feedback inhibition by the end product L-leucine. We characterized the short form IPMS from Leptospira biflexa (LbIPMS2), which exhibits a catalytic activity comparable with that of the long form IPMS (LbIPMS1) and has a similar N-terminal domain followed by subdomain I and subdomain II but lacks the whole C-terminal regulatory domain. We found that partial deletion of the regulatory domain of LbIPMS1 resulted in a loss of about 50% of the catalytic activity; however, when the regulatory domain was deleted up to Arg-385, producing a protein that is almost equivalent to the intact LbIPMS2, about 90% of the activity was maintained. Moreover, in LbIPMS2 or LbIPMS1, further deletion of several residues from the C terminus of subdomain II significantly impaired or completely abolished the catalytic activity, respectively. These results define a complete and independently functional catalytic module of IPMS consisting of both the N-terminal domain and the two subdomains. Structural comparison of LbIPMS2 and the Mycobacterium tuberculosis IPMS revealed two different conformations of subdomain II that likely represent two substrate-binding states related to cooperative catalysis. The biochemical and structural analyses together with the previously published hydrogen-deuterium exchange data led us to propose a conformation transition mechanism for feedback inhibition mediated by subdomains I and II that might associated with alteration of the binding affinity toward acetyl-CoA. Subdomain II of alpha-isopropylmalate synthase is essential for activity: inferring a mechanism of feedback inhibition.,Zhang Z, Wu J, Lin W, Wang J, Yan H, Zhao W, Ma J, Ding J, Zhang P, Zhao GP J Biol Chem. 2014 Oct 3;289(40):27966-78. doi: 10.1074/jbc.M114.559716. Epub 2014, Aug 15. PMID:25128527[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||