2dqu
From Proteopedia
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| - | [[Image:2dqu.gif|left|200px]] | + | [[Image:2dqu.gif|left|200px]] |
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| - | '''Crystal form II: high resolution crystal structure of the complex of the hydrolytic antibody Fab 6D9 and a transition-state analog''' | + | {{Structure |
| + | |PDB= 2dqu |SIZE=350|CAPTION= <scene name='initialview01'>2dqu</scene>, resolution 1.70Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CPD:[1-(3-DIMETHYLAMINO-PROPYL)-3-ETHYL-UREIDO]-[4-(2,2,2-TRIFLUORO-ACETYLAMINO)-BENZYL]PHOSPHINIC ACID-2-(2,2-DIHYDRO-ACETYLAMINO)-3-HYDROXY-1-(4-NITROPHENYL)-PROPYL ESTER'>CPD</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
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| + | '''Crystal form II: high resolution crystal structure of the complex of the hydrolytic antibody Fab 6D9 and a transition-state analog''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2DQU is a [ | + | 2DQU is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry 1HYY. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DQU OCA]. |
==Reference== | ==Reference== | ||
| - | Thermodynamic and structural basis for transition-state stabilization in antibody-catalyzed hydrolysis., Oda M, Ito N, Tsumuraya T, Suzuki K, Sakakura M, Fujii I, J Mol Biol. 2007 May 25;369(1):198-209. Epub 2007 Mar 15. PMID:[http:// | + | Thermodynamic and structural basis for transition-state stabilization in antibody-catalyzed hydrolysis., Oda M, Ito N, Tsumuraya T, Suzuki K, Sakakura M, Fujii I, J Mol Biol. 2007 May 25;369(1):198-209. Epub 2007 Mar 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17428500 17428500] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: immunoglobulin]] | [[Category: immunoglobulin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:30:21 2008'' |
Revision as of 14:30, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal form II: high resolution crystal structure of the complex of the hydrolytic antibody Fab 6D9 and a transition-state analog
Overview
Catalytic antibodies 6D9 and 9C10, which were induced by immunization with a haptenic transition-state analog (TSA), catalyze the hydrolysis of a nonbioactive chloramphenicol monoester derivative to generate a bioactive chloramphenicol. These antibodies stabilize the transition state to catalyze the hydrolysis reaction, strictly according to the theoretical relationship: for 6D9, k(cat)/k(uncat)=895 and K(S)/K(TSA)=900, and for 9C10, k(cat)/k(uncat)=56 and K(S)/K(TSA)=60. To elucidate the molecular basis of the antibody-catalyzed reaction, the crystal structure of 6D9 was determined, and the binding thermodynamics of 6D9 and 9C10 with both the substrate and the TSA were analyzed using isothermal titration calorimetry. The crystal structure of the unliganded 6D9 Fab was determined at 2.25 A resolution and compared with that of the TSA-liganded 6D9 Fab reported previously, showing that the TSA is bound into the hydrophobic pocket of the antigen-combining site in an "induced fit" manner, especially at the L1 and H3 CDR loops. Thermodynamic analyses showed that 6D9 binds the substrate of the TSA with a positive DeltaS, differing from general thermodynamic characteristics of antigen-antibody interactions. This positive DeltaS could be due to the hydrophobic interactions between 6D9 and the substrate or the TSA mediated by Trp H100i. The difference in DeltaG between substrate and TSA-binding to 6D9 was larger than that to 9C10, which is in good correlation with the larger k(cat) value of 6D9. Interestingly, the DeltaDeltaG was mainly because of the DeltaDeltaH. The correlation between k(cat) and DeltaDeltaH is suggestive of "enthalpic strain" leading to destabilization of antibody-substrate complexes. Together with X-ray structural analyses, the thermodynamic analyses suggest that upon binding the substrate, the antibody alters the conformation of the ester moiety in the substrate from the planar Z form to a thermodynamically unstable twisted conformation, followed by conversion into the transition state. Enthalpic strain also contributes to the transition-state stabilization by destabilizing the ground state, and its degree is much larger for the more efficient catalytic antibody, 6D9.
About this Structure
2DQU is a Protein complex structure of sequences from Mus musculus. This structure supersedes the now removed PDB entry 1HYY. Full crystallographic information is available from OCA.
Reference
Thermodynamic and structural basis for transition-state stabilization in antibody-catalyzed hydrolysis., Oda M, Ito N, Tsumuraya T, Suzuki K, Sakakura M, Fujii I, J Mol Biol. 2007 May 25;369(1):198-209. Epub 2007 Mar 15. PMID:17428500
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