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PDBsum entry 3caj

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Lyase PDB id
3caj
Jmol
Contents
Protein chain
258 a.a.
Ligands
EZL
MBO
GOL
Metals
_ZN
_CL
Waters ×303

References listed in PDB file
Key reference
Title Carbonic anhydrase inhibitors: the X-Ray crystal structure of ethoxzolamide complexed to human isoform ii reveals the importance of thr200 and gln92 for obtaining tight-Binding inhibitors.
Authors A.Di fiore, C.Pedone, J.Antel, H.Waldeck, A.Witte, M.Wurl, A.Scozzafava, C.T.Supuran, G.De simone.
Ref. Bioorg Med Chem Lett, 2008, 18, 2669-2674. [DOI no: 10.1016/j.bmcl.2008.03.023]
PubMed id 18359629
Abstract
Ethoxzolamide, an almost forgotten inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), is the only classical inhibitor whose structure in adduct with any isoform was not reported yet. We report here the inhibition data of this molecule with the 12 catalytically active mammalian isozymes (CA I-CA XIV) and the X-ray crystal structure with the cytosolic, ubiquitous isoform CA II. These data are presumably useful for the design of novel CA inhibitors, targeting various CA isozymes, considering that ethoxzolamide was already the lead molecule to obtain the second generation inhibitors, dorzolamide and brinzolamide, clinically used antiglaucoma agents with topical action, as well as various other investigational agents.
Secondary reference #1
Title Positions of his-64 and a bound water in human carbonic anhydrase ii upon binding three structurally related inhibitors.
Authors G.M.Smith, R.S.Alexander, D.W.Christianson, B.M.Mckeever, G.S.Ponticello, J.P.Springer, W.C.Randall, J.J.Baldwin, C.N.Habecker.
Ref. Protein Sci, 1994, 3, 118-125. [DOI no: 10.1002/pro.5560030115]
PubMed id 8142888
Full text Abstract
Figure 1.
Fig. 1. Inhibitorstructures la, Ib, and IC, showing the numbering scheme used or of theinhibitors and referenced in Table 2.
Figure 4.
Fig. 4. Stereo views of the 1F, 1 - IF, I omit contoured at 20 for inhibitors la (A), Ib (B), and IC (C).
The above figures are reproduced from the cited reference which is an Open Access publication published by the Protein Society
Secondary reference #2
Title Structures of murine carbonic anhydrase IV and human carbonic anhydrase ii complexed with brinzolamide: molecular basis of isozyme-Drug discrimination.
Authors T.Stams, Y.Chen, P.A.Boriack-Sjodin, J.D.Hurt, J.Liao, J.A.May, T.Dean, P.Laipis, D.N.Silverman, D.W.Christianson.
Ref. Protein Sci, 1998, 7, 556-563. [DOI no: 10.1002/pro.5560070303]
PubMed id 9541386
Full text Abstract
Figure 6.
Fig. 6. Differenceelectrondensitymap of thehumanCAII-brinzolamide complex,generatedwithFouriercoefficients IF,I - I,] nd phasescal- culatedfromthefnalmodelminustheatoms of brinzolamide(contoured at 3~ ). Thesulfonamidenitrogen of brinzolamide coordinates tozncand displaces zinc-boundhydroxide,therebymaintainingtetrahedralmetalco- ordinationgeometry.Thealiphatictail of brinzolamidemakesvander Waals contactwihPhe-131and Pro-202.
Figure 8.
Fig. 8. CAII-brinzolamide and CAIV-brinzolamide complexes (upper left and lower right, respectively). Brinzolamide is magenta; the CAIV- membrane interaction is represented schematically, where the GPI anchor (yellow) attached to the C-terminus of the enzyme is inserted into the CAIV orientation by interacting with negatively charged phosphates (red). Figure prepared with MOLSCRIPT (Kraulis, 1991) and Raster 3D (Bacon & Anderson, 1988; Merritt & Murphy, 1994).
The above figures are reproduced from the cited reference which is an Open Access publication published by the Protein Society
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