6h9e: Difference between revisions

Revision as of 06:20, 26 October 2022

Structure of glutamate mutase reconstituted with homo-coenzyme B12

Structural highlights

6h9e is a 4 chain structure with sequence from Clostridium cochlearium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	B12, FWK, GOL, TAR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GMSS_CLOCO Catalyzes the carbon skeleton rearrangement of L-glutamate to L-threo-3-methylaspartate ((2S,3S)-3-methylaspartate).[HAMAP-Rule:MF_00526]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Catalysis by radical enzymes dependent on coenzyme B12 (AdoCbl) relies on the reactive primary 5'-deoxy-5'adenosyl radical, which originates from reversible Co-C bond homolysis of AdoCbl. This bond homolysis is accelerated roughly 10(12) -fold upon binding the enzyme substrate. The structural basis for this activation is still strikingly enigmatic. As revealed here, a displaced firm adenosine binding cavity in substrate-loaded glutamate mutase (GM) causes a structural misfit for intact AdoCbl that is relieved by the homolytic Co-C bond cleavage. Strategically interacting adjacent adenosine- and substrate-binding protein cavities provide a tight caged radical reaction space, controlling the entire radical path. The GM active site is perfectly structured for promoting radical catalysis, including "negative catalysis", a paradigm for AdoCbl-dependent mutases.

Structure-Based Demystification of Radical Catalysis by a Coenzyme B12 Dependent Enzyme-Crystallographic Study of Glutamate Mutase with Cofactor Homologues.,Gruber K, Csitkovits V, Lyskowski A, Kratky C, Krautler B Angew Chem Int Ed Engl. 2022 Aug 26;61(35):e202208295. doi:, 10.1002/anie.202208295. Epub 2022 Jul 21. PMID:35793207^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Leutbecher U, Bocher R, Linder D, Buckel W. Glutamate mutase from Clostridium cochlearium. Purification, cobamide content and stereospecific inhibitors. Eur J Biochem. 1992 Apr 15;205(2):759-65. PMID:1315276
↑ Zelder O, Beatrix B, Leutbecher U, Buckel W. Characterization of the coenzyme-B12-dependent glutamate mutase from Clostridium cochlearium produced in Escherichia coli. Eur J Biochem. 1994 Dec 1;226(2):577-85. PMID:7880251
↑ Zelder O, Beatrix B, Buckel W. Cloning, sequencing and expression in Escherichia coli of the gene encoding component S of the coenzyme B12-dependent glutamate mutase from Clostridium cochlearium. FEMS Microbiol Lett. 1994 May 1;118(1-2):15-21. PMID:8013871
↑ Gruber K, Csitkovits V, Lyskowski A, Kratky C, Krautler B. Structure-Based Demystification of Radical Catalysis by a Coenzyme B12 Dependent Enzyme-Crystallographic Study of Glutamate Mutase with Cofactor Homologues. Angew Chem Int Ed Engl. 2022 Aug 26;61(35):e202208295. doi:, 10.1002/anie.202208295. Epub 2022 Jul 21. PMID:35793207 doi:https://dx.doi.org/10.1002/anie.202208295

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OCA

[1] Leutbecher U, Bocher R, Linder D, Buckel W. Glutamate mutase from Clostridium cochlearium. Purification, cobamide content and stereospecific inhibitors. Eur J Biochem. 1992 Apr 15;205(2):759-65. PMID:1315276

[2] Zelder O, Beatrix B, Leutbecher U, Buckel W. Characterization of the coenzyme-B12-dependent glutamate mutase from Clostridium cochlearium produced in Escherichia coli. Eur J Biochem. 1994 Dec 1;226(2):577-85. PMID:7880251

[3] Zelder O, Beatrix B, Buckel W. Cloning, sequencing and expression in Escherichia coli of the gene encoding component S of the coenzyme B12-dependent glutamate mutase from Clostridium cochlearium. FEMS Microbiol Lett. 1994 May 1;118(1-2):15-21. PMID:8013871

[4] Gruber K, Csitkovits V, Lyskowski A, Kratky C, Krautler B. Structure-Based Demystification of Radical Catalysis by a Coenzyme B12 Dependent Enzyme-Crystallographic Study of Glutamate Mutase with Cofactor Homologues. Angew Chem Int Ed Engl. 2022 Aug 26;61(35):e202208295. doi:, 10.1002/anie.202208295. Epub 2022 Jul 21. PMID:35793207 doi:https://dx.doi.org/10.1002/anie.202208295

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[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='6h9e' size='340' side='right'caption='[[6h9e]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6h9e]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H9E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H9E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6h9e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_cochlearium Clostridium cochlearium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6H9E FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B12:COBALAMIN'>B12</scene>, <scene name='pdbligand=FWK:(2~{R},3~{R},4~{S},5~{R})-2-(6-aminopurin-9-yl)-5-ethyl-oxolane-3,4-diol'>FWK</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B12:COBALAMIN'>B12</scene>, <scene name='pdbligand=FWK:(2~{R},3~{R},4~{S},5~{R})-2-(6-aminopurin-9-yl)-5-ethyl-oxolane-3,4-diol'>FWK</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methylaspartate_mutase Methylaspartate mutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.1 5.4.99.1] </span></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=6h9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h9e OCA], [https://pdbe.org/6h9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6h9e RCSB], [https://www.ebi.ac.uk/pdbsum/6h9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6h9e ProSAT]</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=6h9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h9e OCA], [http://pdbe.org/6h9e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h9e RCSB], [http://www.ebi.ac.uk/pdbsum/6h9e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h9e ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GMSS_CLOCO GMSS_CLOCO]] Catalyzes the carbon skeleton rearrangement of L-glutamate to L-threo-3-methylaspartate ((2S,3S)-3-methylaspartate).[HAMAP-Rule:MF_00526]<ref>PMID:1315276</ref> <ref>PMID:7880251</ref> <ref>PMID:8013871</ref>  [[http://www.uniprot.org/uniprot/GLME_CLOCO GLME_CLOCO]] Catalyzes the carbon skeleton rearrangement of L-glutamate to L-threo-3-methylaspartate ((2S,3S)-3-methylaspartate).<ref>PMID:7880251</ref> <ref>PMID:1315276</ref>
+[https://www.uniprot.org/uniprot/GMSS_CLOCO GMSS_CLOCO] Catalyzes the carbon skeleton rearrangement of L-glutamate to L-threo-3-methylaspartate ((2S,3S)-3-methylaspartate).[HAMAP-Rule:MF_00526]<ref>PMID:1315276</ref> <ref>PMID:7880251</ref> <ref>PMID:8013871</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Catalysis by radical enzymes dependent on coenzyme B12 (AdoCbl) relies on the reactive primary 5'-deoxy-5'adenosyl radical, which originates from reversible Co-C bond homolysis of AdoCbl. This bond homolysis is accelerated roughly 10(12) -fold upon binding the enzyme substrate. The structural basis for this activation is still strikingly enigmatic. As revealed here, a displaced firm adenosine binding cavity in substrate-loaded glutamate mutase (GM) causes a structural misfit for intact AdoCbl that is relieved by the homolytic Co-C bond cleavage. Strategically interacting adjacent adenosine- and substrate-binding protein cavities provide a tight caged radical reaction space, controlling the entire radical path. The GM active site is perfectly structured for promoting radical catalysis, including "negative catalysis", a paradigm for AdoCbl-dependent mutases.
+Structure-Based Demystification of Radical Catalysis by a Coenzyme B12 Dependent Enzyme-Crystallographic Study of Glutamate Mutase with Cofactor Homologues.,Gruber K, Csitkovits V, Lyskowski A, Kratky C, Krautler B Angew Chem Int Ed Engl. 2022 Aug 26;61(35):e202208295. doi:, 10.1002/anie.202208295. Epub 2022 Jul 21. PMID:35793207<ref>PMID:35793207</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6h9e" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Clostridium cochlearium]]
 [[Category: Large Structures]]
-[[Category: Methylaspartate mutase]]
+[[Category: Csitkovits V]]
-[[Category: Csitkovits, V]]
+[[Category: Gruber K]]
-[[Category: Gruber, K]]
+[[Category: Kratky C]]
-[[Category: Kratky, C]]
-[[Category: Co-c-bond]]
-[[Category: Coenzyme b12]]
-[[Category: Isomerase]]
-[[Category: Radical reaction]]
-[[Category: Rossman-fold]]
-[[Category: Tim-barrel]]

6h9e: Difference between revisions

Revision as of 06:20, 26 October 2022

Structure of glutamate mutase reconstituted with homo-coenzyme B12

Structural highlights

Function

Publication Abstract from PubMed

References

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