1hq5: Difference between revisions

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New page: left|200px<br /><applet load="1hq5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hq5, resolution 2.3Å" /> '''CRYSTAL STRUCTURE OF ...
 
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[[Image:1hq5.jpg|left|200px]]<br /><applet load="1hq5" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1hq5, resolution 2.3&Aring;" />
'''CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH S-(2-BORONOETHYL)-L-CYSTEINE, AN L-ARGININE ANALOGUE'''<br />


==Overview==
==CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH S-(2-BORONOETHYL)-L-CYSTEINE, AN L-ARGININE ANALOGUE==
The boronic acid-based arginine analogue S-(2-boronoethyl)-L-cysteine, (BEC) has been synthesized and assayed as a slow-binding competitive, inhibitor of the binuclear manganese metalloenzyme arginase. Kinetic, measurements indicate a K(I) value of 0.4-0.6 microM, which is in, reasonable agreement with the dissociation constant of 2.22 microM, measured by isothermal titration calorimetry. The X-ray crystal structure, of the arginase-BEC complex has been determined at 2.3 A resolution from, crystals perfectly twinned by hemihedry. The structure of the complex, reveals that the boronic acid moiety undergoes nucleophilic attack by, metal-bridging hydroxide ion to yield a tetrahedral boronate anion that, bridges the binuclear manganese cluster, thereby mimicking the tetrahedral, intermediate (and its flanking transition states) in the arginine, hydrolysis reaction. Accordingly, the binding mode of BEC is consistent, with the structure-based mechanism proposed for arginase as outlined in, Cox et al. [Cox, J. D., Cama, E., Colleluori D. M., Pethe, S., Boucher, J., S., Mansuy, D., Ash, D. E., and Christianson, D. W. (2001) Biochemistry, 40, 2689-2701.]. Since BEC does not inhibit nitric oxide synthase, BEC, serves as a valuable reagent to probe the physiological relationship, between arginase and nitric oxide (NO) synthase in regulating the, NO-dependent smooth muscle relaxation in human penile corpus cavernosum, tissue that is required for erection. Consequently, we demonstrate that, arginase is present in human penile corpus cavernosum tissue, and that the, arginase inhibitor BEC causes significant enhancement of NO-dependent, smooth muscle relaxation in this tissue. Therefore, human penile arginase, is a potential target for the treatment of sexual dysfunction in the male.
<StructureSection load='1hq5' size='340' side='right'caption='[[1hq5]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1hq5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HQ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HQ5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=S2C:S-2-(BORONOETHYL)-L-CYSTEINE'>S2C</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hq5 OCA], [https://pdbe.org/1hq5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hq5 RCSB], [https://www.ebi.ac.uk/pdbsum/1hq5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hq5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ARGI1_RAT ARGI1_RAT]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hq/1hq5_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hq5 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1HQ5 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 S2C 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HQ5 OCA].
*[[Arginase 3D structures|Arginase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Probing erectile function: S-(2-boronoethyl)-L-cysteine binds to arginase as a transition state analogue and enhances smooth muscle relaxation in human penile corpus cavernosum., Kim NN, Cox JD, Baggio RF, Emig FA, Mistry SK, Harper SL, Speicher DW, Morris SM Jr, Ash DE, Traish A, Christianson DW, Biochemistry. 2001 Mar 6;40(9):2678-88. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11258879 11258879]
[[Category: Large Structures]]
[[Category: Arginase]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Ash DE]]
[[Category: Ash, D.E.]]
[[Category: Baggio RF]]
[[Category: Baggio, R.F.]]
[[Category: Christianson DW]]
[[Category: Christianson, D.W.]]
[[Category: Cox JD]]
[[Category: Cox, J.D.]]
[[Category: Emig FA]]
[[Category: Emig, F.A.]]
[[Category: Harper SL]]
[[Category: Harper, S.L.]]
[[Category: Kim NN]]
[[Category: Jr., S.M.Morris.]]
[[Category: Mistry SK]]
[[Category: Kim, N.N.]]
[[Category: Morris Jr SM]]
[[Category: Mistry, S.K.]]
[[Category: Speicher DW]]
[[Category: Speicher, D.W.]]
[[Category: Traish A]]
[[Category: Traish, A.]]
[[Category: MN]]
[[Category: S2C]]
[[Category: binuclear manganese cluster]]
[[Category: boronic acid inhibitor]]
[[Category: perfectly twinned crystal]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 16:44:15 2007''

Latest revision as of 10:29, 7 February 2024

CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH S-(2-BORONOETHYL)-L-CYSTEINE, AN L-ARGININE ANALOGUECRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH S-(2-BORONOETHYL)-L-CYSTEINE, AN L-ARGININE ANALOGUE

Structural highlights

1hq5 is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ARGI1_RAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1hq5, resolution 2.30Å

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