PDBsum entry 2ajs

Immune system

PDB id

2ajs

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Contents

			Protein chains

					216 a.a. *


					219 a.a. *

			Ligands

					GOL ×4


					SO4


					P33

			Waters ×405

* Residue conservation analysis

PDB id:

2ajs

Links

Name:

Immune system

Title:

Crystal structure of cocaine catalytic antibody 7a1 fab' in complex with heptaethylene glycol

Structure:

Antibody 7a1 fab'. Chain: l. Fragment: immunoglobulin igg1 kappa light chain. Antibody 7a1 fab'. Chain: h. Fragment: immunoglobulin igg1 heavy chain

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090

Biol. unit:

Dimer (from PQS)

Resolution:

1.70Å

R-factor:

0.209

R-free:

0.233

Authors:

X.Zhu,I.A.Wilson

Key ref:

X.Zhu et al. (2006). Complete reaction cycle of a cocaine catalytic antibody at atomic resolution. Structure, 14, 205-216. PubMed id: 16472740 DOI: 10.1016/j.str.2005.10.014

Date:

02-Aug-05

Release date:

14-Feb-06

PROCHECK

	Headers

	References

Protein chain

P01837 (IGKC_MOUSE) - Immunoglobulin kappa constant from Mus musculus

Seq: Struc:					107 a.a. 216 a.a.

Protein chain

Q5M842 (Q5M842_RAT) - IgG-2a protein from Rattus norvegicus

Seq: Struc:					458 a.a. 219 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 56 residue positions (black crosses)

DOI no: 10.1016/j.str.2005.10.014	Structure 14:205-216 (2006)
PubMed id: 16472740

Complete reaction cycle of a cocaine catalytic antibody at atomic resolution.
X.Zhu, T.J.Dickerson, C.J.Rogers, G.F.Kaufmann, J.M.Mee, K.M.McKenzie, K.D.Janda, I.A.Wilson.

ABSTRACT

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.

Selected figure(s)



	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).

Figure was selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

18417480

E.W.Debler, R.Müller, D.Hilvert, and I.A.Wilson (2008).
Conformational isomerism can limit antibody catalysis.

J Biol Chem, 283, 16554-16560.

PDB codes:

3cfj 3cfk

18341277

Y.Pan, D.Gao, and C.G.Zhan (2008).
Modeling the catalysis of anti-cocaine catalytic antibody: competing reaction pathways and free energy barriers.

J Am Chem Soc, 130, 5140-5149.

17400249

E.W.Debler, G.F.Kaufmann, R.N.Kirchdoerfer, J.M.Mee, K.D.Janda, and I.A.Wilson (2007).
Crystal structures of a quorum-quenching antibody.

J Mol Biol, 368, 1392-1402.

PDB codes:

2ntf 2op4

17084858

K.M.McKenzie, J.M.Mee, C.J.Rogers, M.S.Hixon, G.F.Kaufmann, and K.D.Janda (2007).
Identification and characterization of single chain anti-cocaine catalytic antibodies.

J Mol Biol, 365, 722-731.

17444523

L.Premkumar, C.L.Rife, S.Sri Krishna, D.McMullan, M.D.Miller, P.Abdubek, E.Ambing, T.Astakhova, H.L.Axelrod, J.M.Canaves, D.Carlton, H.J.Chiu, T.Clayton, M.DiDonato, L.Duan, M.A.Elsliger, J.Feuerhelm, R.Floyd, S.K.Grzechnik, J.Hale, E.Hampton, G.W.Han, J.Haugen, L.Jaroszewski, K.K.Jin, H.E.Klock, M.W.Knuth, E.Koesema, J.S.Kovarik, A.Kreusch, I.Levin, T.M.McPhillips, A.T.Morse, E.Nigoghossian, L.Okach, S.Oommachen, J.Paulsen, K.Quijano, R.Reyes, F.Rezezadeh, D.Rodionov, R.Schwarzenbacher, G.Spraggon, H.van den Bedem, A.White, G.Wolf, Q.Xu, K.O.Hodgson, J.Wooley, A.M.Deacon, A.Godzik, S.A.Lesley, and I.A.Wilson (2007).
Crystal structure of TM1030 from Thermotoga maritima at 2.3 A resolution reveals molecular details of its transcription repressor function.

Proteins, 68, 418-424.

PDB code:

1zkg

17131989

C.J.Rogers, L.M.Eubanks, T.J.Dickerson, and K.D.Janda (2006).
Unexpected acetylcholinesterase activity of cocaine esterases.

J Am Chem Soc, 128, 15364-15365.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.