1hq5: Difference between revisions

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Revision as of 12:40, 20 March 2008

File:1hq5.jpg

, resolution 2.3Å

Ligands:

and

Activity:

Arginase, with EC number 3.5.3.1

Coordinates:

save as pdb, mmCIF, xml

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

OverviewOverview

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.

About this StructureAbout this Structure

1HQ5 is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

ReferenceReference

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:11258879

Page seeded by OCA on Thu Mar 20 11:40:13 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1hq5.jpg|left|200px]]<br /><applet load="1hq5" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1hq5.jpg|left|200px]]
-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 />
+ {{Structure
+|PDB= 1hq5 |SIZE=350|CAPTION= <scene name='initialview01'>1hq5</scene>, resolution 2.3&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> and <scene name='pdbligand=S2C:S-2-(BORONOETHYL)-L-CYSTEINE'>S2C</scene>
+|ACTIVITY= [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]
+|GENE=
+}}
+'''CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH S-(2-BORONOETHYL)-L-CYSTEINE, AN L-ARGININE ANALOGUE'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-HQ5 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=S2C:'>S2C</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=1HQ5 OCA].
+HQ5 is a [[Single protein]] structure of sequence from [http://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].
 ==Reference==
-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]
+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://www.ncbi.nlm.nih.gov/pubmed/11258879 11258879]
 [[Category: Arginase]]
 [[Category: Rattus norvegicus]]
@@ Line 31: / Line 40: @@
 [[Category: perfectly twinned crystal]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:03:44 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:40:13 2008''