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PDBsum entry 2ajz
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Immune system
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PDB id
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2ajz
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References listed in PDB file
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Key reference
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Title
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Complete reaction cycle of a cocaine catalytic antibody at atomic resolution.
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Authors
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X.Zhu,
T.J.Dickerson,
C.J.Rogers,
G.F.Kaufmann,
J.M.Mee,
K.M.Mckenzie,
K.D.Janda,
I.A.Wilson.
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Ref.
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Structure, 2006,
14,
205-216.
[DOI no: ]
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PubMed id
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Abstract
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Antibody 7A1 hydrolyzes cocaine to produce nonpsychoactive metabolites ecgonine
methyl ester and benzoic acid. Crystal structures of 7A1 Fab' and six complexes
with substrate cocaine, the transition state analog, products ecgonine methyl
ester and benzoic acid together and individually, as well as heptaethylene
glycol have been analyzed at 1.5-2.3 A resolution. Here, we present snapshots of
the complete cycle of the cocaine hydrolytic reaction at atomic resolution.
Significant structural rearrangements occur along the reaction pathway, but they
are generally limited to the binding site, including the ligands themselves.
Several interacting side chains either change their rotamers or alter their
mobility to accommodate the different reaction steps. CDR loop movements (up to
2.3 A) and substantial side chain rearrangements (up to 9 A) alter the shape and
size ( approximately 320-500 A(3)) of the antibody active site from
"open" to "closed" to "open" for the substrate,
transition state, and product states, respectively.
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Figure 2.
Figure 2. Crystal Structure of the 7A1 Fab' Cocaine Complex
with the C[a] Trace of the Antibody Light and Heavy Chains
Colored in Light and Dark Gray, Respectively
CDRs L1, L2,
and L3 are colored brown, while CDRs H1, H2, and H3 are colored
blue. Substrate cocaine is also shown with yellow carbons in the
active site. All of the figures were generated in Bobscript
(Esnouf, 1999) and rendered in Raster3D (Merritt and Murphy,
1994).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2006,
14,
205-216)
copyright 2006.
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