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< | ==Gabaculien complex of gabaculine resistant GSAM version== | ||
<StructureSection load='3fqa' size='340' side='right'caption='[[3fqa]], [[Resolution|resolution]] 2.35Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3fqa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synechococcus_elongatus_PCC_6301 Synechococcus elongatus PCC 6301]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FQA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FQA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GAB:3-AMINOBENZOIC+ACID'>GAB</scene>, <scene name='pdbligand=PMP:4-DEOXY-4-AMINOPYRIDOXAL-5-PHOSPHATE'>PMP</scene></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=3fqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fqa OCA], [https://pdbe.org/3fqa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fqa RCSB], [https://www.ebi.ac.uk/pdbsum/3fqa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fqa ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GSA_SYNP6 GSA_SYNP6] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fq/3fqa_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fqa ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Gabaculine is a potent inhibitor of the vitamin B6-dependent key enzyme in chlorophyll biosynthesis, glutamate-1-semialdehyde aminomutase (GSAM). The inhibition effect is caused by an enzymatic deprotonation of the neurotoxin and requires the aldimine (PLP) form of the cofactor at the active site. In this study, we show that a single-point mutation confers resistance to gabaculine. A combined functional and structural analysis of wild-type GSAM in complex with gabaculine and the GSAM(M248I) form allowed us to decipher in atomic detail the molecular basis of this unique resistance. Interestingly, the gabaculine tolerance is caused by the absence of an essential water molecule that has a dual functional role. It serves as a nucleophilic shuttle for the hydroxyl anion along the reaction pathway and holds active-site Lys273 in a catalytically competent conformation. The single-point mutant is not able to fix this catalytic water between the beta-branched side chain of Ile248 and Lys273. As a consequence, the mutant enzyme is trapped in a gabaculine-insensitive but still enzymatically active amine (PMP) form. | |||
Absence of a catalytic water confers resistance to the neurotoxin gabaculine.,Orriss GL, Patel TR, Sorensen J, Stetefeld J FASEB J. 2010 Feb;24(2):404-14. Epub 2009 Sep 28. PMID:19786580<ref>PMID:19786580</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3fqa" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Aminomutase 3D structures|Aminomutase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[Category: Synechococcus elongatus PCC 6301]] | |||
[[Category: Stetefeld J]] | |||
== | |||
< | |||
[[Category: | |||
[[Category: Synechococcus elongatus | |||
[[Category: Stetefeld | |||
Latest revision as of 09:50, 6 September 2023
Gabaculien complex of gabaculine resistant GSAM versionGabaculien complex of gabaculine resistant GSAM version
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedGabaculine is a potent inhibitor of the vitamin B6-dependent key enzyme in chlorophyll biosynthesis, glutamate-1-semialdehyde aminomutase (GSAM). The inhibition effect is caused by an enzymatic deprotonation of the neurotoxin and requires the aldimine (PLP) form of the cofactor at the active site. In this study, we show that a single-point mutation confers resistance to gabaculine. A combined functional and structural analysis of wild-type GSAM in complex with gabaculine and the GSAM(M248I) form allowed us to decipher in atomic detail the molecular basis of this unique resistance. Interestingly, the gabaculine tolerance is caused by the absence of an essential water molecule that has a dual functional role. It serves as a nucleophilic shuttle for the hydroxyl anion along the reaction pathway and holds active-site Lys273 in a catalytically competent conformation. The single-point mutant is not able to fix this catalytic water between the beta-branched side chain of Ile248 and Lys273. As a consequence, the mutant enzyme is trapped in a gabaculine-insensitive but still enzymatically active amine (PMP) form. Absence of a catalytic water confers resistance to the neurotoxin gabaculine.,Orriss GL, Patel TR, Sorensen J, Stetefeld J FASEB J. 2010 Feb;24(2):404-14. Epub 2009 Sep 28. PMID:19786580[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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