Structure determination of murine mitochondrial carbonic anhydrase V at 2.45-A resolution: implications for catalytic proton transfer and inhibitor design - PubMed (original) (raw)

Structure determination of murine mitochondrial carbonic anhydrase V at 2.45-A resolution: implications for catalytic proton transfer and inhibitor design

P A Boriack-Sjodin et al. Proc Natl Acad Sci U S A. 1995.

Abstract

The three-dimensional structure of murine mitochondrial carbonic anhydrase V has been determined and refined at 2.45-A resolution (crystallographic R factor = 0.187). Significant structural differences unique to the active site of carbonic anhydrase V are responsible for differences in the mechanism of catalytic proton transfer as compared with other carbonic anhydrase isozymes. In the prototypical isozyme, carbonic anhydrase II, catalytic proton transfer occurs via the shuttle group His-64; carbonic anhydrase V has Tyr-64, which is not an efficient proton shuttle due in part to the bulky adjacent side chain of Phe-65. Based on analysis of the structure of carbonic anhydrase V, we speculate that Tyr-131 may participate in proton transfer due to its proximity to zinc-bound solvent, its solvent accessibility, and its electrostatic environment in the protein structure. Finally, the design of isozyme-specific inhibitors is discussed in view of the complex between carbonic anhydrase V and acetazolamide, a transition-state analogue. Such inhibitors may be physiologically important in the regulation of blood glucose levels.

PubMed Disclaimer

Cited by

Stabilization of anionic and neutral forms of a fluorophoric ligand at the active site of human carbonic anhydrase I.
Manokaran S, Banerjee J, Mallik S, Srivastava DK. Manokaran S, et al. Biochim Biophys Acta. 2010 Oct;1804(10):1965-73. doi: 10.1016/j.bbapap.2010.06.024. Epub 2010 Jul 8. Biochim Biophys Acta. 2010. PMID: 20620244 Free PMC article.
Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells.
Whittington DA, Waheed A, Ulmasov B, Shah GN, Grubb JH, Sly WS, Christianson DW. Whittington DA, et al. Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9545-50. doi: 10.1073/pnas.161301298. Epub 2001 Aug 7. Proc Natl Acad Sci U S A. 2001. PMID: 11493685 Free PMC article.
A plant-type (beta-class) carbonic anhydrase in the thermophilic methanoarchaeon Methanobacterium thermoautotrophicum.
Smith KS, Ferry JG. Smith KS, et al. J Bacteriol. 1999 Oct;181(20):6247-53. doi: 10.1128/JB.181.20.6247-6253.1999. J Bacteriol. 1999. PMID: 10515911 Free PMC article.
Insights towards sulfonamide drug specificity in α-carbonic anhydrases.
Aggarwal M, Kondeti B, McKenna R. Aggarwal M, et al. Bioorg Med Chem. 2013 Mar 15;21(6):1526-33. doi: 10.1016/j.bmc.2012.08.019. Epub 2012 Aug 28. Bioorg Med Chem. 2013. PMID: 22985956 Free PMC article.
Structural and kinetic characterization of an archaeal beta-class carbonic anhydrase.
Smith KS, Cosper NJ, Stalhandske C, Scott RA, Ferry JG. Smith KS, et al. J Bacteriol. 2000 Dec;182(23):6605-13. doi: 10.1128/JB.182.23.6605-6613.2000. J Bacteriol. 2000. PMID: 11073902 Free PMC article.

References

1. J Lab Clin Med. 1983 Oct;102(4):536-42 - PubMed
1. Arch Biochem Biophys. 1986 Nov 15;251(1):198-204 - PubMed
1. J Mol Biol. 1992 Oct 20;227(4):1192-204 - PubMed
1. Arch Biochem Biophys. 1959 Mar;81(1):124-9 - PubMed
1. Biochemistry. 1989 Sep 19;28(19):7913-8 - PubMed

Structure determination of murine mitochondrial carbonic anhydrase V at 2.45-A resolution: implications for catalytic proton transfer and inhibitor design - PubMed (original) (raw)