1hq5: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1hq5.jpg|left|200px]] | [[Image:1hq5.jpg|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1hq5", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
| | --> | ||
| | {{STRUCTURE_1hq5| PDB=1hq5 | SCENE= }} | ||
}} | |||
'''CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH S-(2-BORONOETHYL)-L-CYSTEINE, AN L-ARGININE ANALOGUE''' | '''CRYSTAL STRUCTURE OF THE BINUCLEAR MANGANESE METALLOENZYME ARGINASE COMPLEXED WITH S-(2-BORONOETHYL)-L-CYSTEINE, AN L-ARGININE ANALOGUE''' | ||
| Line 37: | Line 34: | ||
[[Category: Speicher, D W.]] | [[Category: Speicher, D W.]] | ||
[[Category: Traish, A.]] | [[Category: Traish, A.]] | ||
[[Category: | [[Category: Binuclear manganese cluster]] | ||
[[Category: | [[Category: Boronic acid inhibitor]] | ||
[[Category: | [[Category: Perfectly twinned crystal]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:06:44 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 19:06, 2 May 2008
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 Fri May 2 19:06:44 2008