1can
From Proteopedia
(New page: 200px<br /> <applet load="1can" size="450" color="white" frame="true" align="right" spinBox="true" caption="1can, resolution 1.9Å" /> '''CRYSTALLOGRAPHIC STU...) |
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caption="1can, resolution 1.9Å" /> | caption="1can, resolution 1.9Å" /> | ||
'''CRYSTALLOGRAPHIC STUDIES OF THE BINDING OF PROTONATED AND UNPROTONATED INHIBITORS TO CARBONIC ANHYDRASE USING HYDROGEN SULPHIDE AND NITRATE ANIONS'''<br /> | '''CRYSTALLOGRAPHIC STUDIES OF THE BINDING OF PROTONATED AND UNPROTONATED INHIBITORS TO CARBONIC ANHYDRASE USING HYDROGEN SULPHIDE AND NITRATE ANIONS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structures of human carbonic-anhydrase-II complexes with the anionic | + | The structures of human carbonic-anhydrase-II complexes with the anionic inhibitors hydrogen sulphide (HS-) and nitrate (NO3-) have been determined by X-ray diffraction at 0.19-nm resolution from crystals soaked at pH 7.8 and 6.0, respectively. The modes of binding of these two anions differ markedly from each other. The strong inhibitor HS- replaces the native zinc-bound water/hydroxide (Wat263) leaving the tetrahedral metal geometry unaltered and acts as a hydrogen-bonding donor towards Thr199 gamma. The weak NO3- inhibitor does not displace Wat263 from the metal coordination but occupies a fifth binding site changing the zinc coordination polyhedron into a slightly distorted trigonal bipyramid. The interaction of NO3- with the metal is weak; the nearest of its oxygen atoms being at a distance of 0.28 nm from the zinc ion. The binding of nitrate to the enzyme is completed by a hydrogen bond to the metal coordinated Wat263 and a second one to a water molecule of the active-site cavity. The structures of the two complexes help to rationalize the binding of anionic inhibitors to carbonic anhydrase and the binding mode displayed by NO39 may be relevant to the catalytic mechanism. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1CAN 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 HG, NO3 and ACE as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1CAN 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=HG:'>HG</scene>, <scene name='pdbligand=NO3:'>NO3</scene> and <scene name='pdbligand=ACE:'>ACE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1CAN OCA]. |
==Reference== | ==Reference== | ||
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[[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 12:04:12 2008'' |
Revision as of 10:04, 21 February 2008
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CRYSTALLOGRAPHIC STUDIES OF THE BINDING OF PROTONATED AND UNPROTONATED INHIBITORS TO CARBONIC ANHYDRASE USING HYDROGEN SULPHIDE AND NITRATE ANIONS
Contents |
Overview
The structures of human carbonic-anhydrase-II complexes with the anionic inhibitors hydrogen sulphide (HS-) and nitrate (NO3-) have been determined by X-ray diffraction at 0.19-nm resolution from crystals soaked at pH 7.8 and 6.0, respectively. The modes of binding of these two anions differ markedly from each other. The strong inhibitor HS- replaces the native zinc-bound water/hydroxide (Wat263) leaving the tetrahedral metal geometry unaltered and acts as a hydrogen-bonding donor towards Thr199 gamma. The weak NO3- inhibitor does not displace Wat263 from the metal coordination but occupies a fifth binding site changing the zinc coordination polyhedron into a slightly distorted trigonal bipyramid. The interaction of NO3- with the metal is weak; the nearest of its oxygen atoms being at a distance of 0.28 nm from the zinc ion. The binding of nitrate to the enzyme is completed by a hydrogen bond to the metal coordinated Wat263 and a second one to a water molecule of the active-site cavity. The structures of the two complexes help to rationalize the binding of anionic inhibitors to carbonic anhydrase and the binding mode displayed by NO39 may be relevant to the catalytic mechanism.
Disease
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[611492]
About this Structure
1CAN is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Crystallographic studies of the binding of protonated and unprotonated inhibitors to carbonic anhydrase using hydrogen sulphide and nitrate anions., Mangani S, Hakansson K, Eur J Biochem. 1992 Dec 15;210(3):867-71. PMID:1336460
Page seeded by OCA on Thu Feb 21 12:04:12 2008
Categories: Carbonate dehydratase | Homo sapiens | Single protein | Hakansson, K. | Mangani, S. | ACE | HG | NO3 | Lyase(oxo-acid)
