1d6s
From Proteopedia
(New page: 200px<br /><applet load="1d6s" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d6s, resolution 2.30Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1d6s.gif|left|200px]]<br /><applet load="1d6s" size=" | + | [[Image:1d6s.gif|left|200px]]<br /><applet load="1d6s" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1d6s, resolution 2.30Å" /> | caption="1d6s, resolution 2.30Å" /> | ||
'''CRYSTAL STRUCTURE OF THE K41A MUTANT OF O-ACETYLSERINE SULFHYDRYLASE COMPLEXED IN EXTERNAL ALDIMINE LINKAGE WITH METHIONINE'''<br /> | '''CRYSTAL STRUCTURE OF THE K41A MUTANT OF O-ACETYLSERINE SULFHYDRYLASE COMPLEXED IN EXTERNAL ALDIMINE LINKAGE WITH METHIONINE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Covalent binding of L-methionine as an external aldimine to the pyridoxal | + | Covalent binding of L-methionine as an external aldimine to the pyridoxal 5'-phosphate-cofactor in the K41A mutant of O-acetylserine sulfhydrylase from Salmonella typhimurium induces a large conformational change in the protein. Methionine mimics the action of the substrate O-acetyl-L-serine during catalysis. The alpha-carboxylate moiety of L-methionine in external aldimine linkage with the active site pyridoxal 5'-phosphate forms a hydrogen bonding network to the "asparagine-loop" P67-T68-N69-G70 which adopts a different conformation than in the native protein. The side-chain nitrogen of Asn69 moves more than 7 A to make a hydrogen bond to the alpha-carboxylate group of the inhibitor. As the external aldimine is formed, the PLP tilts by 13 degrees along its longitudinal axis such that C4' moves toward the entrance to the active site and the side-chain of the methionine is directed toward the active site entrance. The local rearrangement acts as a trigger to induce a large global conformational change in the protein. A subdomain comprised of beta-strand 4, alpha-helix 3, beta-strand 5 and alpha-helix 4 moves towards the active site by a rotation of 7 degrees. This subdomain movement results in a reduction of the severe twist of its central beta-sheet and reduces the active site entrance to a small hole, giving access only to small molecules like sulfide, the second substrate, or acetate, the first product. |
==About this Structure== | ==About this Structure== | ||
| - | 1D6S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium] with MET and PLP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cysteine_synthase Cysteine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.47 2.5.1.47] Full crystallographic information is available from [http:// | + | 1D6S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium] with <scene name='pdbligand=MET:'>MET</scene> and <scene name='pdbligand=PLP:'>PLP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cysteine_synthase Cysteine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.47 2.5.1.47] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D6S OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Burkhard, P.]] | [[Category: Burkhard, P.]] | ||
| - | [[Category: Cook, P | + | [[Category: Cook, P F.]] |
| - | [[Category: Jansonius, J | + | [[Category: Jansonius, J N.]] |
| - | [[Category: Ristroph, C | + | [[Category: Ristroph, C M.]] |
| - | [[Category: Tai, C | + | [[Category: Tai, C H.]] |
[[Category: MET]] | [[Category: MET]] | ||
[[Category: PLP]] | [[Category: PLP]] | ||
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[[Category: plp]] | [[Category: plp]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:13:36 2008'' |
Revision as of 10:13, 21 February 2008
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CRYSTAL STRUCTURE OF THE K41A MUTANT OF O-ACETYLSERINE SULFHYDRYLASE COMPLEXED IN EXTERNAL ALDIMINE LINKAGE WITH METHIONINE
Overview
Covalent binding of L-methionine as an external aldimine to the pyridoxal 5'-phosphate-cofactor in the K41A mutant of O-acetylserine sulfhydrylase from Salmonella typhimurium induces a large conformational change in the protein. Methionine mimics the action of the substrate O-acetyl-L-serine during catalysis. The alpha-carboxylate moiety of L-methionine in external aldimine linkage with the active site pyridoxal 5'-phosphate forms a hydrogen bonding network to the "asparagine-loop" P67-T68-N69-G70 which adopts a different conformation than in the native protein. The side-chain nitrogen of Asn69 moves more than 7 A to make a hydrogen bond to the alpha-carboxylate group of the inhibitor. As the external aldimine is formed, the PLP tilts by 13 degrees along its longitudinal axis such that C4' moves toward the entrance to the active site and the side-chain of the methionine is directed toward the active site entrance. The local rearrangement acts as a trigger to induce a large global conformational change in the protein. A subdomain comprised of beta-strand 4, alpha-helix 3, beta-strand 5 and alpha-helix 4 moves towards the active site by a rotation of 7 degrees. This subdomain movement results in a reduction of the severe twist of its central beta-sheet and reduces the active site entrance to a small hole, giving access only to small molecules like sulfide, the second substrate, or acetate, the first product.
About this Structure
1D6S is a Single protein structure of sequence from Salmonella typhimurium with and as ligands. Active as Cysteine synthase, with EC number 2.5.1.47 Full crystallographic information is available from OCA.
Reference
Ligand binding induces a large conformational change in O-acetylserine sulfhydrylase from Salmonella typhimurium., Burkhard P, Tai CH, Ristroph CM, Cook PF, Jansonius JN, J Mol Biol. 1999 Aug 27;291(4):941-53. PMID:10452898
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