1d3v
From Proteopedia
(New page: 200px<br /><applet load="1d3v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d3v, resolution 1.70Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1d3v.gif|left|200px]]<br /><applet load="1d3v" size=" | + | [[Image:1d3v.gif|left|200px]]<br /><applet load="1d3v" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1d3v, resolution 1.70Å" /> | caption="1d3v, resolution 1.70Å" /> | ||
'''CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH 2(S)-AMINO-6-BORONOHEXANOIC ACID, AN L-ARGININE ANALOG'''<br /> | '''CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH 2(S)-AMINO-6-BORONOHEXANOIC ACID, AN L-ARGININE ANALOG'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of the complex between the binuclear manganese | + | The crystal structure of the complex between the binuclear manganese metalloenzyme arginase and the boronic acid analog of L-arginine, 2(S)-amino-6-boronohexanoic acid (ABH), has been determined at 1.7 A resolution from a crystal perfectly twinned by hemihedry. ABH binds as the tetrahedral boronate anion, with one hydroxyl oxygen symmetrically bridging the binuclear manganese cluster and a second hydroxyl oxygen coordinating to Mn2+A. This binding mode mimics the transition state of a metal-activated hydroxide mechanism. This transition state structure differs from that occurring in NO biosynthesis, thereby explaining why ABH does not inhibit NO synthase. We also show that arginase activity is present in the penis. Accordingly, the tight binding and specificity of ABH allows us to probe the physiological role of arginase in modulating the NO-dependent smooth muscle relaxation required for erection. Strikingly, ABH causes significant enhancement of nonadrenergic, noncholinergic nerve-mediated relaxation of penile corpus cavernosum smooth muscle, suggesting that arginase inhibition sustains L-arginine concentrations for NO synthase activity. Therefore, human penile arginase is a potential target for therapeutic intervention in the treatment of erectile dysfunction. |
==About this Structure== | ==About this Structure== | ||
| - | 1D3V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with MN and ABH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Arginase Arginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.1 3.5.3.1] Full crystallographic information is available from [http:// | + | 1D3V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=MN:'>MN</scene> and <scene name='pdbligand=ABH:'>ABH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Arginase Arginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.1 3.5.3.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D3V OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Christianson, D | + | [[Category: Christianson, D W.]] |
| - | [[Category: Cox, J | + | [[Category: Cox, J D.]] |
| - | [[Category: Kim, N | + | [[Category: Kim, N N.]] |
| - | [[Category: Traish, A | + | [[Category: Traish, A M.]] |
[[Category: ABH]] | [[Category: ABH]] | ||
[[Category: MN]] | [[Category: MN]] | ||
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[[Category: perfectly twinned crystal]] | [[Category: perfectly twinned crystal]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:12:42 2008'' |
Revision as of 10:12, 21 February 2008
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CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH 2(S)-AMINO-6-BORONOHEXANOIC ACID, AN L-ARGININE ANALOG
Overview
The crystal structure of the complex between the binuclear manganese metalloenzyme arginase and the boronic acid analog of L-arginine, 2(S)-amino-6-boronohexanoic acid (ABH), has been determined at 1.7 A resolution from a crystal perfectly twinned by hemihedry. ABH binds as the tetrahedral boronate anion, with one hydroxyl oxygen symmetrically bridging the binuclear manganese cluster and a second hydroxyl oxygen coordinating to Mn2+A. This binding mode mimics the transition state of a metal-activated hydroxide mechanism. This transition state structure differs from that occurring in NO biosynthesis, thereby explaining why ABH does not inhibit NO synthase. We also show that arginase activity is present in the penis. Accordingly, the tight binding and specificity of ABH allows us to probe the physiological role of arginase in modulating the NO-dependent smooth muscle relaxation required for erection. Strikingly, ABH causes significant enhancement of nonadrenergic, noncholinergic nerve-mediated relaxation of penile corpus cavernosum smooth muscle, suggesting that arginase inhibition sustains L-arginine concentrations for NO synthase activity. Therefore, human penile arginase is a potential target for therapeutic intervention in the treatment of erectile dysfunction.
About this Structure
1D3V is a Single protein structure of sequence from Rattus norvegicus with and as ligands. Active as Arginase, with EC number 3.5.3.1 Full crystallographic information is available from OCA.
Reference
Arginase-boronic acid complex highlights a physiological role in erectile function., Cox JD, Kim NN, Traish AM, Christianson DW, Nat Struct Biol. 1999 Nov;6(11):1043-7. PMID:10542097
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