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| [[Image:1dca.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1dca| PDB=1dca | SCENE= }} | | {{STRUCTURE_1dca| PDB=1dca | SCENE= }} |
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| '''STRUCTURE OF AN ENGINEERED METAL BINDING SITE IN HUMAN CARBONIC ANHYDRASE II REVEALS THE ARCHITECTURE OF A REGULATORY CYSTEINE SWITCH'''
| | ===STRUCTURE OF AN ENGINEERED METAL BINDING SITE IN HUMAN CARBONIC ANHYDRASE II REVEALS THE ARCHITECTURE OF A REGULATORY CYSTEINE SWITCH=== |
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| ==Overview==
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| X-ray crystallographic analysis of the Thr-199-->Cys (T199C) variant of human carbonic anhydrase II reveals the first high-resolution structure of an engineered zinc coordination polyhedron in a metalloenzyme. In the wild-type enzyme, Thr-199 accepts a hydrogen bond from zinc-bound hydroxide; in the variant, the polypeptide backbone is sufficiently plastic to permit Cys-199 to displace hydroxide ion and coordinate to zinc with nearly perfect coordination stereochemistry. Importantly, the resulting His3-Cys-Zn2+ motif binds zinc more tightly than the wild-type enzyme [Kiefer, L. L., Krebs, J. F., Paterno, S. A., & Fierke C. A. (1993) Biochemistry (preceding paper in this issue)]. This novel zinc coordination polyhedron is analogous to that postulated for matrix metalloproteinase zymogens such as prostromelysin, where a cysteine-zinc interaction is responsible for the inactivity of the zymogen. Intriguingly, Cys-199 of T199C CAII is displaced from zinc coordination by soaking crystals in high concentrations of acetazolamide. Hence, residual catalytic activity measured for this variant probably arises from an alternate conformer of Cys-199 which allows the catalytic nucleophile, hydroxide ion, to be activated by zinc coordination.
| | The line below this paragraph, {{ABSTRACT_PUBMED_8399159}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 8399159 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_8399159}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Christianson, D W.]] | | [[Category: Christianson, D W.]] |
| [[Category: Ippolito, J A.]] | | [[Category: Ippolito, J A.]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:41:01 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 22:48:45 2008'' |
