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PDBsum entry 2ca2
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Lyase(oxo-acid)
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PDB id
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2ca2
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References listed in PDB file
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Key reference
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Title
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Crystallographic studies of inhibitor binding sites in human carbonic anhydrase ii: a pentacoordinated binding of the scn- Ion to the zinc at high ph.
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Authors
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A.E.Eriksson,
P.M.Kylsten,
T.A.Jones,
A.Liljas.
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Ref.
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Proteins, 1988,
4,
283-293.
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PubMed id
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Abstract
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The binding of four inhibitors--mercuric ion,
3-acetoxymercuri-4-aminobenzenesulfonamide (AMS), acetazolamide (Diamox), and
thiocyanate ion--to human carbonic anhydrase II (HCA II) has been studied with
X-ray crystallography. The binding of mercury to HCA II at pH 7.0 has been
investigated at 3.1 A resolution. Mercuric ions are observed at both nitrogens
in the His-64 ring. One of these sites is pointing toward the zinc ion. The only
other binding site for mercury is at Cys-206. The binding of the two sulfonamide
inhibitors AMS and Diamox, has been reinvestigated at 2.0 and 3.0 A,
respectively. Only the nitrogen of the sulfonamide group binds to the zinc ion
replacing the hydroxyl ion. The sulfonamide oxygen closest to the zinc ion is
3.1 A away. Thus the tetrahedral geometry of the zinc is retained, refuting
earlier models of a pentacoordinated zinc. The structure of the thiocyanate
complex has been investigated at pH 8.5 and the structure has been refined at
1.9 A resolution using the least-squares refinement program PROLSQ. The
crystallographic R factor is 17.6%. The zinc ion is pentacoordinated with the
anion as well as a water molecule bound in addition to the three histidine
residues. The nitrogen atom of the SCN- ion is 1.9 A from the zinc ion but
shifted 1.3 A with respect to the hydroxyl ion in the native structure and at
van der Waals' distance from the O gamma l atom of Thr-199. This is due to the
inability of the O gamma l atom of Thr-199 to serve as a hydrogen bond donor,
thus repelling the nonprotonated nitrogen. The SCN- molecule reaches into the
deep end of the active site cavity where the sulfur atom has displaced the
so-called "deep" water molecule of the native enzyme. The zinc-bound water
molecule is 2.2 A from the zinc ion and 2.4 A from the SCN- nitrogen. In
addition, this water is hydrogen bonded to the O gamma l atom of Thr-199 and to
another water molecule. We have observed that solvent and inhibitor molecules
have three possible binding sites on the zinc ion and their significance for the
catalysis and inhibition of HCA II will be discussed. All available
crystallographic data are consistent with a proposed catalytic mechanism in
which both the OH moiety and one oxygen of the substrate HCO3- ion are ligated
to the zinc ion.
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Secondary reference #1
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Title
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Refined structure of human carbonic anhydrase ii at 2.0 a resolution.
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Authors
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A.E.Eriksson,
T.A.Jones,
A.Liljas.
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Ref.
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Proteins, 1988,
4,
274-282.
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PubMed id
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Secondary reference #2
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Title
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Structural relationship of human erythrocyte carbonic anhydrase isozymes b and c
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Authors
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B.Notstrand,
I.Vaara,
K.K.Kannan.
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Ref.
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isozymes-molecular structure, 1975,
1,
575.
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Secondary reference #3
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Title
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Crystal structure of human erythrocyte carbonic anhydrase c. Vi. The three-Dimensional structure at high resolution in relation to other mammalian carbonic anhydrases.
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Authors
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K.K.Kannan,
A.Liljas,
I.Waara,
P.C.Bergstén,
S.Lövgren,
B.Strandberg,
U.Bengtsson,
U.Carlbom,
K.Fridborg,
L.Järup,
M.Petef.
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Ref.
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Cold Spring Harb Symp Quant Biol, 1972,
36,
221-231.
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PubMed id
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Secondary reference #4
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Title
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Crystal structure of human carbonic anhydrase c.
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Authors
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A.Liljas,
K.K.Kannan,
P.C.Bergstén,
I.Waara,
K.Fridborg,
B.Strandberg,
U.Carlbom,
L.Järup,
S.Lövgren,
M.Petef.
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Ref.
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Nat New Biol, 1972,
235,
131-137.
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PubMed id
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