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| | {{STRUCTURE_43c9| PDB=43c9 | SCENE= }} | | {{STRUCTURE_43c9| PDB=43c9 | SCENE= }} |
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| - | '''CRYSTALLOGRAPHIC STRUCTURE OF THE ESTEROLYTIC AND AMIDOLYTIC 43C9 ANTIBODY'''
| + | ===CRYSTALLOGRAPHIC STRUCTURE OF THE ESTEROLYTIC AND AMIDOLYTIC 43C9 ANTIBODY=== |
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| - | ==Overview==
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| - | Among catalytic antibodies, the well-characterized antibody 43C9 is unique in its ability to catalyze the difficult, but desirable, reaction of selective amide hydrolysis. The crystallographic structures that we present here for the single-chain variable fragment of the 43C9 antibody, both with and without the bound product p -nitrophenol, strongly support and extend the structural and mechanistic information previously provided by a three-dimensional computational model, together with extensive biochemical, kinetics, and mutagenesis results. The structures reveal an unexpected extended beta-sheet conformation of the third complementarity determining region of the heavy chain, which may be coupled to the novel indole ring orientation of the adjacent Trp H103. This unusual conformation creates an antigen-binding site that is significantly deeper than predicted in the computational model, with a hydrophobic pocket that encloses the p -nitrophenol product. Despite these differences, the previously proposed roles for Arg L96 in transition-state stabilization and for His L91 as the nucleophile that forms a covalent acyl-antibody intermediate are fully supported by the crystallographic structures. His L91 is now centered at the bottom of the antigen-binding site with the imidazole ring poised for nucleophilic attack. His L91, Arg L96, and the bound p -nitrophenol are linked into a hydrogen-bonding network by two well-ordered water molecules. These water molecules may mimic the positions of the phosphonamidate oxygen atoms of the antigen, which in turn mimic the transition state of the reaction. This network also contains His H35, suggesting that this residue may also stabilize the transition-states. A possible proton-transfer pathway from His L91 through two tyrosine residues may assist nucleophilic attack. Although transition-state stabilization is commonly observed in esterolytic antibodies, nucleophilic attack appears to be unique to 43C9 and accounts for the unusually high catalytic activity of this antibody.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10438624}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10438624 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10438624}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Thayer, M M.]] | | [[Category: Thayer, M M.]] |
| | [[Category: Immunoglobulin]] | | [[Category: Immunoglobulin]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:17:58 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 13:20:02 2008'' |
Revision as of 10:20, 3 July 2008
Template:STRUCTURE 43c9
CRYSTALLOGRAPHIC STRUCTURE OF THE ESTEROLYTIC AND AMIDOLYTIC 43C9 ANTIBODY
Template:ABSTRACT PUBMED 10438624
About this Structure
43C9 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Structural basis for amide hydrolysis catalyzed by the 43C9 antibody., Thayer MM, Olender EH, Arvai AS, Koike CK, Canestrelli IL, Stewart JD, Benkovic SJ, Getzoff ED, Roberts VA, J Mol Biol. 1999 Aug 13;291(2):329-45. PMID:10438624
Page seeded by OCA on Thu Jul 3 13:20:02 2008
