|
|
| (One intermediate revision by the same user not shown) |
| Line 1: |
Line 1: |
|
| |
|
| ==Isopropylmalate synthase binding with ketoisovalerate== | | ==Isopropylmalate synthase binding with ketoisovalerate== |
| <StructureSection load='4ov4' size='340' side='right' caption='[[4ov4]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='4ov4' size='340' side='right'caption='[[4ov4]], [[Resolution|resolution]] 2.00Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4ov4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lepbp Lepbp]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OV4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OV4 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4ov4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leptospira_biflexa_serovar_Patoc_strain_'Patoc_1_(Paris)' Leptospira biflexa serovar Patoc strain 'Patoc 1 (Paris)']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OV4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OV4 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KIV:3-METHYL-2-OXOBUTANOIC+ACID'>KIV</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ov9|4ov9]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KIV:3-METHYL-2-OXOBUTANOIC+ACID'>KIV</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IPMS2, LEPBI_I1108, leuA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=456481 LEPBP])</td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ov4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ov4 OCA], [https://pdbe.org/4ov4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ov4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ov4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ov4 ProSAT]</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://pdbe.org/4ov4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ov4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ov4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ov4 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/B0SN40_LEPBP B0SN40_LEPBP] |
| 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>
| |
|
| |
|
| ==See Also== | | ==See Also== |
| *[[2-isopropylmalate synthase|2-isopropylmalate synthase]] | | *[[2-isopropylmalate synthase 3D structures|2-isopropylmalate synthase 3D structures]] |
| == References ==
| |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: 2-isopropylmalate synthase]] | | [[Category: Large Structures]] |
| [[Category: Lepbp]]
| | [[Category: Wang C]] |
| [[Category: Wang, C]] | | [[Category: Wu J]] |
| [[Category: Wu, J]] | | [[Category: Zhang P]] |
| [[Category: Zhang, P]] | | [[Category: Zhang Z]] |
| [[Category: Zhang, Z]] | |
| [[Category: Alpha/beta tim barrel]]
| |
| [[Category: Transferase]]
| |