1znc
From Proteopedia
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|PDB= 1znc |SIZE=350|CAPTION= <scene name='initialview01'>1znc</scene>, resolution 2.8Å | |PDB= 1znc |SIZE=350|CAPTION= <scene name='initialview01'>1znc</scene>, resolution 2.8Å | ||
|SITE= <scene name='pdbsite=CTA:Zn+Coordinated+By+HIS+A+94,+HIS+A+96,+And+HIS+A+119.+Als+...'>CTA</scene> and <scene name='pdbsite=CTB:Zn+Coordinated+By+HIS+B+94,+HIS+B+96,+And+HIS+B+119.+Als+...'>CTB</scene> | |SITE= <scene name='pdbsite=CTA:Zn+Coordinated+By+HIS+A+94,+HIS+A+96,+And+HIS+A+119.+Als+...'>CTA</scene> and <scene name='pdbsite=CTB:Zn+Coordinated+By+HIS+B+94,+HIS+B+96,+And+HIS+B+119.+Als+...'>CTB</scene> | ||
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= HUMAN CAIV ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= HUMAN CAIV ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1znc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1znc OCA], [http://www.ebi.ac.uk/pdbsum/1znc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1znc RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
It has recently been demonstrated that the C-terminal deletion mutant of recombinant human carbonic anhydrase IV (G267X CA IV) converts the normally glycosylphosphatidylinositol-anchored enzyme into a soluble secretory form which has the same catalytic properties as the membrane-associated enzyme purified from human tissues. We have determined the three-dimensional structure of the secretory form of human CA IV by x-ray crystallographic methods to a resolution of 2.8 A. Although the zinc binding site and the hydrophobic substrate binding pocket of CA IV are generally similar to those of other mammalian isozymes, unique structural differences are found elsewhere in the active site. Two disufide linkages, Cys-6-Cys-11G and Cys-23-Cys-203, stabilize the conformation of the N-terminal domain. The latter disulfide additionally stabilizes an active site loop containing a cis-peptide linkage between Pro-201 and Thr-202 (this loop contains catalytic residue Thr-199). On the opposite side of the active site, the Val-131-Asp-136 segment adopts an extended loop conformation instead of an alpha-helix conformation as found in other isozymes. Finally, the C terminus is surrounded by a substantial electropositive surface potential, which is likely to stabilize the interaction of CA IV with the negatively charged phospholipid headgroups of the membrane. These structural features are unique to CA IV and provide a framework for the design of sulfonamide inhibitors selective for this particular isozyme. | It has recently been demonstrated that the C-terminal deletion mutant of recombinant human carbonic anhydrase IV (G267X CA IV) converts the normally glycosylphosphatidylinositol-anchored enzyme into a soluble secretory form which has the same catalytic properties as the membrane-associated enzyme purified from human tissues. We have determined the three-dimensional structure of the secretory form of human CA IV by x-ray crystallographic methods to a resolution of 2.8 A. Although the zinc binding site and the hydrophobic substrate binding pocket of CA IV are generally similar to those of other mammalian isozymes, unique structural differences are found elsewhere in the active site. Two disufide linkages, Cys-6-Cys-11G and Cys-23-Cys-203, stabilize the conformation of the N-terminal domain. The latter disulfide additionally stabilizes an active site loop containing a cis-peptide linkage between Pro-201 and Thr-202 (this loop contains catalytic residue Thr-199). On the opposite side of the active site, the Val-131-Asp-136 segment adopts an extended loop conformation instead of an alpha-helix conformation as found in other isozymes. Finally, the C terminus is surrounded by a substantial electropositive surface potential, which is likely to stabilize the interaction of CA IV with the negatively charged phospholipid headgroups of the membrane. These structural features are unique to CA IV and provide a framework for the design of sulfonamide inhibitors selective for this particular isozyme. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Retinitis pigmentosa-17 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114760 114760]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Christianson, D W.]] | [[Category: Christianson, D W.]] | ||
[[Category: Stams, T.]] | [[Category: Stams, T.]] | ||
| - | [[Category: SO4]] | ||
| - | [[Category: ZN]] | ||
[[Category: gpi-anchor]] | [[Category: gpi-anchor]] | ||
[[Category: lyase]] | [[Category: lyase]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:39:09 2008'' |
Revision as of 22:39, 30 March 2008
| |||||||
| , resolution 2.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | , | ||||||
| Gene: | HUMAN CAIV (Homo sapiens) | ||||||
| Activity: | Carbonate dehydratase, with EC number 4.2.1.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN CARBONIC ANHYDRASE IV
Overview
It has recently been demonstrated that the C-terminal deletion mutant of recombinant human carbonic anhydrase IV (G267X CA IV) converts the normally glycosylphosphatidylinositol-anchored enzyme into a soluble secretory form which has the same catalytic properties as the membrane-associated enzyme purified from human tissues. We have determined the three-dimensional structure of the secretory form of human CA IV by x-ray crystallographic methods to a resolution of 2.8 A. Although the zinc binding site and the hydrophobic substrate binding pocket of CA IV are generally similar to those of other mammalian isozymes, unique structural differences are found elsewhere in the active site. Two disufide linkages, Cys-6-Cys-11G and Cys-23-Cys-203, stabilize the conformation of the N-terminal domain. The latter disulfide additionally stabilizes an active site loop containing a cis-peptide linkage between Pro-201 and Thr-202 (this loop contains catalytic residue Thr-199). On the opposite side of the active site, the Val-131-Asp-136 segment adopts an extended loop conformation instead of an alpha-helix conformation as found in other isozymes. Finally, the C terminus is surrounded by a substantial electropositive surface potential, which is likely to stabilize the interaction of CA IV with the negatively charged phospholipid headgroups of the membrane. These structural features are unique to CA IV and provide a framework for the design of sulfonamide inhibitors selective for this particular isozyme.
About this Structure
1ZNC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-A resolution., Stams T, Nair SK, Okuyama T, Waheed A, Sly WS, Christianson DW, Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13589-94. PMID:8942978
Page seeded by OCA on Mon Mar 31 01:39:09 2008
