title: Atomic resolution studies of carbonic anhydrase II.
abstract: Carbonic anhydrase has been well studied structurally and functionally owing to its importance in respiration. A large number of X-ray crystallographic structures of carbonic anhydrase and its inhibitor complexes have been determined, some at atomic resolution. Structure determination of a sulfonamide-containing inhibitor complex has been carried out and the structure was refined at 0.9 A resolution with anisotropic atomic displacement parameters to an R value of 0.141. The structure is similar to those of other carbonic anhydrase complexes, with the inhibitor providing a fourth nonprotein ligand to the active-site zinc. Comparison of this structure with 13 other atomic resolution (higher than 1.25 A) isomorphous carbonic anhydrase structures provides a view of the structural similarity and variability in a series of crystal structures. At the center of the protein the structures superpose very well. The metal complexes superpose (with only two exceptions) with standard deviations of 0.01 A in some zinc-protein and zinc-ligand bond lengths. In contrast, regions of structural variability are found on the protein surface, possibly owing to flexibility and disorder in the individual structures, differences in the chemical and crystalline environments or the different approaches used by different investigators to model weak or complicated electron-density maps. These findings suggest that care must be taken in interpreting structural details on protein surfaces on the basis of individual X-ray structures, even if atomic resolution data are available.
authors.affiliation: Department of Biochemistry, University of Washington, Box 357430, Seattle, WA 98195-7430, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Behnke
authors.forename: Isolde
authors.initials: I
authors.lastname: Le Trong
authors.forename: Jeff W
authors.initials: JW
authors.lastname: Godden
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Merritt
authors.forename: David C
authors.initials: DC
authors.lastname: Teller
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bajorath
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Stenkamp
mesh_terms: D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D024402:Carbonic Anhydrase II
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Nov;55(Pt 11):1773-84
references.pmid: 10531472
references.citation: J Struct Biol. 1999 Apr-May;125(2-3):156-65
references.pmid: 10222271
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Jun;55(Pt 6):1109-17
references.pmid: 10329772
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):611-20
references.pmid: 17452786
references.citation: Eur J Biochem. 1975 Nov 1;59(1):253-9
references.pmid: 1249
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: Structure. 2007 Jan;15(1):29-38
references.pmid: 17223530
references.citation: J Mol Biol. 1965 Jul;12(3):740-60
references.pmid: 4955311
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Jul;58(Pt 7):1085-91
references.pmid: 12077426
references.citation: Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22
references.pmid: 18156677
references.citation: Biochemistry. 2007 Mar 20;46(11):2930-7
references.pmid: 17319692
references.citation: J Am Chem Soc. 2007 May 2;129(17):5528-37
references.pmid: 17407288
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 Jan;59(Pt 1):93-104
references.pmid: 12499545
references.citation: Methods Enzymol. 1997;277:505-24
references.pmid: 18488322
references.citation: J Mol Biol. 1992 Oct 20;227(4):1192-204
references.pmid: 1433293
references.citation: J Biol Chem. 2008 Nov 7;283(45):30766-71
references.pmid: 18768466
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Dec;55(Pt 12):1997-2004
references.pmid: 10666575
references.citation: Nat New Biol. 1972 Feb 2;235(57):131-7
references.pmid: 4621826
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jul 1;62(Pt 7):618-22
references.pmid: 16820676
references.citation: J Am Chem Soc. 2006 Mar 8;128(9):3011-8
references.pmid: 16506782