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PDBsum entry 2foq
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Contents |
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* Residue conservation analysis
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Enzyme class 2:
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E.C.4.2.1.1
- carbonic anhydrase.
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Reaction:
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hydrogencarbonate + H+ = CO2 + H2O
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hydrogencarbonate
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+
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H(+)
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=
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CO2
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+
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H2O
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Cofactor:
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Zn(2+)
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Enzyme class 3:
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E.C.4.2.1.69
- cyanamide hydratase.
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Reaction:
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urea = cyanamide + H2O
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urea
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=
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cyanamide
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+
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H2O
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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J Am Chem Soc
128:3011-3018
(2006)
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PubMed id:
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Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors reveal the molecular basis of high affinity.
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K.M.Jude,
A.L.Banerjee,
M.K.Haldar,
S.Manokaran,
B.Roy,
S.Mallik,
D.K.Srivastava,
D.W.Christianson.
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ABSTRACT
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The atomic-resolution crystal structures of human carbonic anhydrases I and II
complexed with "two-prong" inhibitors are reported. Each inhibitor contains a
benzenesulfonamide prong and a cupric iminodiacetate (IDA-Cu(2+)) prong
separated by linkers of different lengths and compositions. The ionized NH(-)
group of each benzenesulfonamide coordinates to the active site Zn(2+) ion; the
IDA-Cu(2+) prong of the tightest-binding inhibitor, BR30, binds to H64 of CAII
and H200 of CAI. This work provides the first evidence verifying the structural
basis of nanomolar affinity measured for two-prong inhibitors targeting the
carbonic anhydrases.
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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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C.A.Behnke,
I.Le Trong,
J.W.Godden,
E.A.Merritt,
D.C.Teller,
J.Bajorath,
and
R.E.Stenkamp
(2010).
Atomic resolution studies of carbonic anhydrase II.
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Acta Crystallogr D Biol Crystallogr,
66,
616-627.
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PDB codes:
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V.Alterio,
S.M.Monti,
E.Truppo,
C.Pedone,
C.T.Supuran,
and
G.De Simone
(2010).
The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex.
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Org Biomol Chem,
8,
3528-3533.
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PDB code:
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E.Meggers
(2009).
Targeting proteins with metal complexes.
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Chem Commun (Camb),
(),
1001-1010.
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K.H.Sippel,
A.H.Robbins,
J.Domsic,
C.Genis,
M.Agbandje-McKenna,
and
R.McKenna
(2009).
High-resolution structure of human carbonic anhydrase II complexed with acetazolamide reveals insights into inhibitor drug design.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
65,
992-995.
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PDB code:
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K.L.Haas,
and
K.J.Franz
(2009).
Application of metal coordination chemistry to explore and manipulate cell biology.
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Chem Rev,
109,
4921-4960.
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V.M.Krishnamurthy,
G.K.Kaufman,
A.R.Urbach,
I.Gitlin,
K.L.Gudiksen,
D.B.Weibel,
and
G.M.Whitesides
(2008).
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.
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Chem Rev,
108,
946.
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A.I.Elegbede,
M.K.Haldar,
S.Manokaran,
J.Kooren,
B.C.Roy,
S.Mallik,
and
D.K.Srivastava
(2007).
A strategy for designing "multi-prong" enzyme inhibitors by incorporating selective ligands to the liposomal surface.
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Chem Commun (Camb),
(),
3377-3379.
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A.I.Elegbede,
M.K.Haldar,
S.Manokaran,
S.Mallik,
and
D.K.Srivastava
(2007).
Recognition of isozymes via lanthanide ion incorporated polymerized liposomes.
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Chem Commun (Camb),
(),
4495-4497.
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D.K.Srivastava,
K.M.Jude,
A.L.Banerjee,
M.Haldar,
S.Manokaran,
J.Kooren,
S.Mallik,
and
D.W.Christianson
(2007).
Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II.
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J Am Chem Soc,
129,
5528-5537.
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PDB codes:
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F.E.Jacobsen,
J.A.Lewis,
and
S.M.Cohen
(2007).
The Design of Inhibitors for Medicinally Relevant Metalloproteins.
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ChemMedChem,
2,
152-171.
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G.E.Höst,
J.Razkin,
L.Baltzer,
and
B.H.Jonsson
(2007).
Combined enzyme and substrate design: grafting of a cooperative two-histidine catalytic motif into a protein targeted at the scissile bond in a designed ester substrate.
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Chembiochem,
8,
1570-1576.
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D.A.Erlanson
(2006).
Fragment-based lead discovery: a chemical update.
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Curr Opin Biotechnol,
17,
643-652.
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H.A.Gennadios,
and
D.W.Christianson
(2006).
Binding of uridine 5'-diphosphate in the "basic patch" of the zinc deacetylase LpxC and implications for substrate binding.
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Biochemistry,
45,
15216-15223.
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PDB codes:
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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
