2q1f
From Proteopedia
(New page: 200px<br /><applet load="2q1f" size="350" color="white" frame="true" align="right" spinBox="true" caption="2q1f, resolution 2.85Å" /> '''Crystal structure of...) |
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caption="2q1f, resolution 2.85Å" /> | caption="2q1f, resolution 2.85Å" /> | ||
'''Crystal structure of chondroitin sulfate lyase abc from bacteroides thetaiotaomicron wal2926'''<br /> | '''Crystal structure of chondroitin sulfate lyase abc from bacteroides thetaiotaomicron wal2926'''<br /> | ||
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| + | ==Overview== | ||
| + | Enzymes have evolved as catalysts with high degrees of stereospecificity., When both enantiomers are biologically important, enzymes with two, different folds usually catalyze reactions with the individual, enantiomers. In rare cases a single enzyme can process both enantiomers, efficiently, but no molecular basis for such catalysis has been, established. The family of bacterial chondroitin lyases ABC is comprised, of such enzymes. They can degrade both chondroitin sulfate (CS) and, dermatan sulfate (DS) glycosaminoglycans at the non-reducing end of either, glucuronic acid (CS) or its epimer iduronic acid (DS) by a, beta-elimination mechanism, which commences with removal of the C-5 proton, from the uronic acid. Two other structural folds evolved to perform these, reactions in an epimer specific fashion: (alpha/alpha)(5) for CS, (chondroitin lyases AC) and beta-helix for DS (chondroitin lyases B);, their catalytic mechanisms have been established at the molecular level., The structure of chondroitinase ABC from Proteus vulgaris showed, surprising similarity to chondroitinase AC, including the presence of a, Tyr-His-Glu-Arg catalytic tetrad, which provided possible mechanism for CS, degradation but not for DS degradation. We determined the structure of a, distantly related Bacteroides thetaiotaomicron chondroitinase ABC to, identify additional structurally conserved residues potentially involved, in catalysis. We found a conserved cluster located approximately 12 A from, the catalytic tetrad. We demonstrate that a histidine in this cluster is, essential for catalysis of DS but not CS. The enzyme utilizes a single, substrate-binding site while having two partially overlapping active sites, catalyzing the respective reactions. The spatial separation of the two, sets of residues suggests a substrate-induced conformational change that, brings all catalytically essential residues close together. | ||
==About this Structure== | ==About this Structure== | ||
| - | 2Q1F is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Chondroitin-sulfate-ABC_endolyase Chondroitin-sulfate-ABC endolyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.2.20 4.2.2.20] Known structural/functional Sites: <scene name='pdbsite=AC1:Ca Binding Site For Residue A 2001'>AC1</scene>, <scene name='pdbsite=AC2:Ca Binding Site For Residue B 2002'>AC2</scene>, <scene name='pdbsite=AC3:Po4 Binding Site For Residue B 2003'>AC3</scene>, <scene name='pdbsite=AC4:Po4 Binding Site For Residue A 2002'>AC4</scene>, <scene name='pdbsite=AC5:Po4 Binding Site For Residue A 2003'>AC5</scene>, <scene name='pdbsite=AC6:Po4 Binding Site For Residue B 2004'>AC6</scene>, <scene name='pdbsite=AC7:Po4 Binding Site For Residue A 2004'>AC7</scene>, <scene name='pdbsite=AC8:Po4 Binding Site For Residue B 2005'>AC8</scene>, <scene name='pdbsite=AC9:Po4 Binding Site For Residue A 2005'>AC9</scene>, <scene name='pdbsite=BC1:Po4 Binding Site For Residue B 2006'>BC1</scene>, <scene name='pdbsite=BC2:Po4 Binding Site For Residue A 2006'>BC2</scene>, <scene name='pdbsite=BC3:Po4 Binding Site For Residue A 2007'>BC3</scene>, <scene name='pdbsite=BC4:Po4 Binding Site For Residue B 2007'>BC4</scene>, <scene name='pdbsite=BC5:Po4 Binding Site For Residue B 2008'>BC5</scene>, <scene name='pdbsite=BC6:Po4 Binding Site For Residue A 2008'>BC6</scene>, <scene name='pdbsite=BC7:Po4 Binding Site For Residue A 2009'>BC7</scene>, <scene name='pdbsite=BC8:Po4 Binding Site For Residue B 2009'>BC8</scene> and <scene name='pdbsite=BC9:Po4 Binding Site For Residue B 2010'>BC9</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q1F OCA]. | + | 2Q1F is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Chondroitin-sulfate-ABC_endolyase Chondroitin-sulfate-ABC endolyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.2.20 4.2.2.20] Known structural/functional Sites: <scene name='pdbsite=AC1:Ca+Binding+Site+For+Residue+A+2001'>AC1</scene>, <scene name='pdbsite=AC2:Ca+Binding+Site+For+Residue+B+2002'>AC2</scene>, <scene name='pdbsite=AC3:Po4+Binding+Site+For+Residue+B+2003'>AC3</scene>, <scene name='pdbsite=AC4:Po4+Binding+Site+For+Residue+A+2002'>AC4</scene>, <scene name='pdbsite=AC5:Po4+Binding+Site+For+Residue+A+2003'>AC5</scene>, <scene name='pdbsite=AC6:Po4+Binding+Site+For+Residue+B+2004'>AC6</scene>, <scene name='pdbsite=AC7:Po4+Binding+Site+For+Residue+A+2004'>AC7</scene>, <scene name='pdbsite=AC8:Po4+Binding+Site+For+Residue+B+2005'>AC8</scene>, <scene name='pdbsite=AC9:Po4+Binding+Site+For+Residue+A+2005'>AC9</scene>, <scene name='pdbsite=BC1:Po4+Binding+Site+For+Residue+B+2006'>BC1</scene>, <scene name='pdbsite=BC2:Po4+Binding+Site+For+Residue+A+2006'>BC2</scene>, <scene name='pdbsite=BC3:Po4+Binding+Site+For+Residue+A+2007'>BC3</scene>, <scene name='pdbsite=BC4:Po4+Binding+Site+For+Residue+B+2007'>BC4</scene>, <scene name='pdbsite=BC5:Po4+Binding+Site+For+Residue+B+2008'>BC5</scene>, <scene name='pdbsite=BC6:Po4+Binding+Site+For+Residue+A+2008'>BC6</scene>, <scene name='pdbsite=BC7:Po4+Binding+Site+For+Residue+A+2009'>BC7</scene>, <scene name='pdbsite=BC8:Po4+Binding+Site+For+Residue+B+2009'>BC8</scene> and <scene name='pdbsite=BC9:Po4+Binding+Site+For+Residue+B+2010'>BC9</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q1F OCA]. |
| + | |||
| + | ==Reference== | ||
| + | Composite Active Site of Chondroitin Lyase ABC Accepting Both Epimers of Uronic Acid., Shaya D, Hahn BS, Bjerkan TM, Kim WS, Park NY, Sim JS, Kim YS, Cygler M, Glycobiology. 2008 Jan 28;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18227125 18227125] | ||
[[Category: Bacteroides thetaiotaomicron]] | [[Category: Bacteroides thetaiotaomicron]] | ||
[[Category: Chondroitin-sulfate-ABC endolyase]] | [[Category: Chondroitin-sulfate-ABC endolyase]] | ||
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[[Category: lyase]] | [[Category: lyase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:18:07 2008'' |
Revision as of 06:18, 13 February 2008
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Crystal structure of chondroitin sulfate lyase abc from bacteroides thetaiotaomicron wal2926
Overview
Enzymes have evolved as catalysts with high degrees of stereospecificity., When both enantiomers are biologically important, enzymes with two, different folds usually catalyze reactions with the individual, enantiomers. In rare cases a single enzyme can process both enantiomers, efficiently, but no molecular basis for such catalysis has been, established. The family of bacterial chondroitin lyases ABC is comprised, of such enzymes. They can degrade both chondroitin sulfate (CS) and, dermatan sulfate (DS) glycosaminoglycans at the non-reducing end of either, glucuronic acid (CS) or its epimer iduronic acid (DS) by a, beta-elimination mechanism, which commences with removal of the C-5 proton, from the uronic acid. Two other structural folds evolved to perform these, reactions in an epimer specific fashion: (alpha/alpha)(5) for CS, (chondroitin lyases AC) and beta-helix for DS (chondroitin lyases B);, their catalytic mechanisms have been established at the molecular level., The structure of chondroitinase ABC from Proteus vulgaris showed, surprising similarity to chondroitinase AC, including the presence of a, Tyr-His-Glu-Arg catalytic tetrad, which provided possible mechanism for CS, degradation but not for DS degradation. We determined the structure of a, distantly related Bacteroides thetaiotaomicron chondroitinase ABC to, identify additional structurally conserved residues potentially involved, in catalysis. We found a conserved cluster located approximately 12 A from, the catalytic tetrad. We demonstrate that a histidine in this cluster is, essential for catalysis of DS but not CS. The enzyme utilizes a single, substrate-binding site while having two partially overlapping active sites, catalyzing the respective reactions. The spatial separation of the two, sets of residues suggests a substrate-induced conformational change that, brings all catalytically essential residues close together.
About this Structure
2Q1F is a Protein complex structure of sequences from Bacteroides thetaiotaomicron with and as ligands. Active as Chondroitin-sulfate-ABC endolyase, with EC number 4.2.2.20 Known structural/functional Sites: , , , , , , , , , , , , , , , , and . Full crystallographic information is available from OCA.
Reference
Composite Active Site of Chondroitin Lyase ABC Accepting Both Epimers of Uronic Acid., Shaya D, Hahn BS, Bjerkan TM, Kim WS, Park NY, Sim JS, Kim YS, Cygler M, Glycobiology. 2008 Jan 28;. PMID:18227125
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