1dcb
From Proteopedia
(New page: 200px<br /> <applet load="1dcb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dcb, resolution 2.1Å" /> '''STRUCTURE OF AN ENGI...) |
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| - | [[Image:1dcb.gif|left|200px]]<br /> | + | [[Image:1dcb.gif|left|200px]]<br /><applet load="1dcb" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1dcb" size=" | + | |
caption="1dcb, resolution 2.1Å" /> | caption="1dcb, resolution 2.1Å" /> | ||
'''STRUCTURE OF AN ENGINEERED METAL BINDING SITE IN HUMAN CARBONIC ANHYDRASE II REVEALS THE ARCHITECTURE OF A REGULATORY CYSTEINE SWITCH'''<br /> | '''STRUCTURE OF AN ENGINEERED METAL BINDING SITE IN HUMAN CARBONIC ANHYDRASE II REVEALS THE ARCHITECTURE OF A REGULATORY CYSTEINE SWITCH'''<br /> | ||
==Overview== | ==Overview== | ||
| - | X-ray crystallographic analysis of the Thr-199-->Cys (T199C) variant of | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DCB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http:// | + | 1DCB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DCB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Christianson, D | + | [[Category: Christianson, D W.]] |
| - | [[Category: Ippolito, J | + | [[Category: Ippolito, J A.]] |
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: lyase(oxo-acid)]] | [[Category: lyase(oxo-acid)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:15:09 2008'' |
Revision as of 10:15, 21 February 2008
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STRUCTURE OF AN ENGINEERED METAL BINDING SITE IN HUMAN CARBONIC ANHYDRASE II REVEALS THE ARCHITECTURE OF A REGULATORY CYSTEINE SWITCH
Contents |
Overview
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.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
1DCB is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Structure of an engineered His3Cys zinc binding site in human carbonic anhydrase II., Ippolito JA, Christianson DW, Biochemistry. 1993 Sep 28;32(38):9901-5. PMID:8399159
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