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* Residue conservation analysis
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Enzyme class:
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Chain L:
E.C.3.2.1.17
- lysozyme.
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Reaction:
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Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.
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DOI no:
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Science
305:1770-1773
(2004)
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PubMed id:
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Crystal structure of a shark single-domain antibody V region in complex with lysozyme.
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R.L.Stanfield,
H.Dooley,
M.F.Flajnik,
I.A.Wilson.
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ABSTRACT
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Cartilaginous fish are the phylogenetically oldest living organisms known to
possess components of the vertebrate adaptive immune system. Key to their immune
response are heavy-chain, homodimeric immunoglobulins called new antigen
receptors (IgNARs), in which the variable (V) domains recognize antigens with
only a single immunoglobulin domain, akin to camelid heavy-chain V domains. The
1.45 angstrom resolution crystal structure of the type I IgNAR V domain in
complex with hen egg-white lysozyme (HEL) reveals a minimal antigen-binding
domain that contains only two of the three conventional
complementarity-determining regions but still binds HEL with nanomolar affinity
by means of a binding interface comparable in size to conventional antibodies.
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Selected figure(s)
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Figure 1.
Fig. 1. Schematic representation of the overall IgG and IgNAR
architectures. (A) A conventional IgG is composed of two H
chains (blue) and two L chains (yellow) that assemble to form
one Fc and two Fab regions or superdomains. The H chain has
three C domains (C[H]1, C[H]2, and C[H]3) and one V domain
(V[H]), whereas the L chain has one C domain (C[L]) and one V
domain (V[L]). The V region is made up of two immunoglobulin
domains (V[H] and V[L]). (B) IgNAR only two H chains, each
consisting of one V and five C domains, where the V domain is
unpaired and constitutes a single-binding module. The IgG and
the IgNAR domains are represented by their harmonic surfaces
generated from atomic coordinates (27); the IgNAR C domains are
represented by ovals because their structures are unknown.
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Figure 3.
Fig. 3. Comparison of the IgNAR V domain with other
immunoglobulin domains. (A) In IgNAR, the front sheet consists
of strands A, B, E, and D, whereas the back sheet consists of
strands A', G, F, and C. The bend between A and A' is similar to
that seen in most V[  ]domains, with a
cis-Pro residue at position N7. (B) IgG V[ ]domain from Fv
B1-8 (PDB accession code 1A6V [PDB]
). (C) TCR V[  ]domain from TCR
KB5-C20 (PDB accession code 1KJ2 [PDB]
). (D) IgG C[L] chain domain from Fab 50.1 (PDB accession code
1GGB [PDB]
). (E) IgG V[H] domain from Fab DB3 (PDB accession code 1DBB [PDB]
) (F) Camel V[L]H domain from cAb-Lys3 (PDB accession code 1JTT
[PDB]
) (27).
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The above figures are
reprinted
by permission from the AAAs:
Science
(2004,
305,
1770-1773)
copyright 2004.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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F.Rahbarizadeh,
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Immunol Invest,
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F.W.Hall,
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(2011).
Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal.
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Proc Natl Acad Sci U S A,
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V.J.Ruigrok,
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Alternative affinity tools: more attractive than antibodies?
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Biochem J,
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L.Deng,
C.A.Velikovsky,
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M.F.Flajnik,
L.Aravind,
Z.Pancer,
and
R.A.Mariuzza
(2010).
A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey.
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Proc Natl Acad Sci U S A,
107,
13408-13413.
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PDB codes:
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R.A.Mariuzza,
C.A.Velikovsky,
L.Deng,
G.Xu,
and
Z.Pancer
(2010).
Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates.
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Biol Chem,
391,
753-760.
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C.A.Velikovsky,
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L.M.Iyer,
M.C.Kerzic,
L.Aravind,
Z.Pancer,
and
R.A.Mariuzza
(2009).
Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen.
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Nat Struct Mol Biol,
16,
725-730.
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PDB codes:
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J.Wesolowski,
V.Alzogaray,
J.Reyelt,
M.Unger,
K.Juarez,
M.Urrutia,
A.Cauerhff,
W.Danquah,
B.Rissiek,
F.Scheuplein,
N.Schwarz,
S.Adriouch,
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M.Seman,
A.Licea,
D.V.Serreze,
F.A.Goldbaum,
F.Haag,
and
F.Koch-Nolte
(2009).
Single domain antibodies: promising experimental and therapeutic tools in infection and immunity.
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Med Microbiol Immunol,
198,
157-174.
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M.Arbabi-Ghahroudi,
R.To,
N.Gaudette,
T.Hirama,
W.Ding,
R.MacKenzie,
and
J.Tanha
(2009).
Aggregation-resistant VHs selected by in vitro evolution tend to have disulfide-bonded loops and acidic isoelectric points.
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Protein Eng Des Sel,
22,
59-66.
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R.Gong,
B.K.Vu,
Y.Feng,
D.A.Prieto,
M.A.Dyba,
J.D.Walsh,
P.Prabakaran,
T.D.Veenstra,
S.G.Tarasov,
R.Ishima,
and
D.S.Dimitrov
(2009).
Engineered human antibody constant domains with increased stability.
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J Biol Chem,
284,
14203-14210.
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S.Tasumi,
C.A.Velikovsky,
G.Xu,
S.A.Gai,
K.D.Wittrup,
M.F.Flajnik,
R.A.Mariuzza,
and
Z.Pancer
(2009).
High-affinity lamprey VLRA and VLRB monoclonal antibodies.
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Proc Natl Acad Sci U S A,
106,
12891-12896.
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D.P.Simmons,
V.A.Streltsov,
O.Dolezal,
P.J.Hudson,
A.M.Coley,
M.Foley,
D.F.Proll,
and
S.D.Nuttall
(2008).
Shark IgNAR antibody mimotopes target a murine immunoglobulin through extended CDR3 loop structures.
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Proteins,
71,
119-130.
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PDB codes:
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E.J.Adams,
P.Strop,
S.Shin,
Y.H.Chien,
and
K.C.Garcia
(2008).
An autonomous CDR3delta is sufficient for recognition of the nonclassical MHC class I molecules T10 and T22 by gammadelta T cells.
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Nat Immunol,
9,
777-784.
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B.Venkatesh,
E.F.Kirkness,
Y.H.Loh,
A.L.Halpern,
A.P.Lee,
J.Johnson,
N.Dandona,
L.D.Viswanathan,
A.Tay,
J.C.Venter,
R.L.Strausberg,
and
S.Brenner
(2007).
Survey sequencing and comparative analysis of the elephant shark (Callorhinchus milii) genome.
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PLoS Biol,
5,
e101.
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G.Kopsidas,
R.K.Carman,
E.L.Stutt,
A.Raicevic,
A.S.Roberts,
M.A.Siomos,
N.Dobric,
L.Pontes-Braz,
and
G.Coia
(2007).
RNA mutagenesis yields highly diverse mRNA libraries for in vitro protein evolution.
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BMC Biotechnol,
7,
18.
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J.L.Liu,
G.P.Anderson,
and
E.R.Goldman
(2007).
Isolation of anti-toxin single domain antibodies from a semi-synthetic spiny dogfish shark display library.
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BMC Biotechnol,
7,
78.
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E.De Genst,
K.Silence,
K.Decanniere,
K.Conrath,
R.Loris,
J.Kinne,
S.Muyldermans,
and
L.Wyns
(2006).
Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies.
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Proc Natl Acad Sci U S A,
103,
4586-4591.
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PDB codes:
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E.Hsu,
N.Pulham,
L.L.Rumfelt,
and
M.F.Flajnik
(2006).
The plasticity of immunoglobulin gene systems in evolution.
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Immunol Rev,
210,
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H.Dooley,
R.L.Stanfield,
R.A.Brady,
and
M.F.Flajnik
(2006).
First molecular and biochemical analysis of in vivo affinity maturation in an ectothermic vertebrate.
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Proc Natl Acad Sci U S A,
103,
1846-1851.
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J.A.Hernández Prada,
R.N.Haire,
M.Allaire,
J.Jakoncic,
V.Stojanoff,
J.P.Cannon,
G.W.Litman,
and
D.A.Ostrov
(2006).
Ancient evolutionary origin of diversified variable regions demonstrated by crystal structures of an immune-type receptor in amphioxus.
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Nat Immunol,
7,
875-882.
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PDB codes:
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M.F.Criscitiello,
M.Saltis,
and
M.F.Flajnik
(2006).
An evolutionarily mobile antigen receptor variable region gene: doubly rearranging NAR-TcR genes in sharks.
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Proc Natl Acad Sci U S A,
103,
5036-5041.
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P.J.Kundrotas,
and
E.Alexov
(2006).
Electrostatic properties of protein-protein complexes.
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Biophys J,
91,
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G.W.Litman,
J.P.Cannon,
and
L.J.Dishaw
(2005).
Reconstructing immune phylogeny: new perspectives.
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Nat Rev Immunol,
5,
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H.Revets,
P.De Baetselier,
and
S.Muyldermans
(2005).
Nanobodies as novel agents for cancer therapy.
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Expert Opin Biol Ther,
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M.Arbabi-Ghahroudi,
J.Tanha,
and
R.MacKenzie
(2005).
Prokaryotic expression of antibodies.
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Cancer Metastasis Rev,
24,
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P.Holliger,
and
P.J.Hudson
(2005).
Engineered antibody fragments and the rise of single domains.
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Nat Biotechnol,
23,
1126-1136.
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R.J.Pleass,
and
A.A.Holder
(2005).
Opinion: antibody-based therapies for malaria.
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Nat Rev Microbiol,
3,
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V.A.Streltsov,
J.A.Carmichael,
and
S.D.Nuttall
(2005).
Structure of a shark IgNAR antibody variable domain and modeling of an early-developmental isotype.
|
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Protein Sci,
14,
2901-2909.
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PDB code:
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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.
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Links
