1wva

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[[Image:1wva.gif|left|200px]]<br /><applet load="1wva" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1wva.gif|left|200px]]
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caption="1wva, resolution 1.94&Aring;" />
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'''Crystal structure of human arginase I from twinned crystal'''<br />
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{{Structure
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|PDB= 1wva |SIZE=350|CAPTION= <scene name='initialview01'>1wva</scene>, resolution 1.94&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> and <scene name='pdbligand=S2C:S-2-(BORONOETHYL)-L-CYSTEINE'>S2C</scene>
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|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]
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|GENE=
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}}
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'''Crystal structure of human arginase I from twinned crystal'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1WVA 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=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=1WVA OCA].
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1WVA is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WVA OCA].
==Reference==
==Reference==
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Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response., Di Costanzo L, Sabio G, Mora A, Rodriguez PC, Ochoa AC, Centeno F, Christianson DW, Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13058-63. Epub 2005 Sep 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16141327 16141327]
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Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response., Di Costanzo L, Sabio G, Mora A, Rodriguez PC, Ochoa AC, Centeno F, Christianson DW, Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13058-63. Epub 2005 Sep 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16141327 16141327]
[[Category: Arginase]]
[[Category: Arginase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: twinned crystal]]
[[Category: twinned crystal]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:48:28 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:01:57 2008''

Revision as of 13:01, 20 March 2008

Image:1wva.gif


PDB ID 1wva

Drag the structure with the mouse to rotate
, resolution 1.94Å
Ligands: and
Activity: Arginase, with EC number 3.5.3.1
Coordinates: save as pdb, mmCIF, xml



Crystal structure of human arginase I from twinned crystal


Overview

Human arginase I is a potential target for therapeutic intervention in diseases linked to compromised l-arginine homeostasis. Here, we report high-affinity binding of the reaction coordinate analogue inhibitors 2(S)-amino-6-boronohexanoic acid (ABH, Kd = 5 nM) and S-(2-boronoethyl)-l-cysteine (BEC, Kd = 270 nM) to human arginase I, and we report x-ray crystal structures of the respective enzyme-inhibitor complexes at 1.29- and 1.94-A resolution determined from crystals twinned by hemihedry. The ultrahigh-resolution structure of the human arginase I-ABH complex yields an unprecedented view of the binuclear manganese cluster and illuminates the structural basis for nanomolar affinity: bidentate inner-sphere boronate-manganese coordination interactions and fully saturated hydrogen bond networks with inhibitor alpha-amino and alpha-carboxylate groups. These interactions are therefore implicated in the stabilization of the transition state for l-arginine hydrolysis. Electron density maps also reveal that active-site residue H141 is protonated as the imidazolium cation. The location of H141 is such that it could function as a general acid to protonate the leaving amino group of l-ornithine during catalysis, and this is a revised mechanistic proposal for arginase. This work serves as a foundation for studying the structural and chemical biology of arginase I in the immune response, and we demonstrate the inhibition of arginase activity by ABH in human and murine myeloid cells.

About this Structure

1WVA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response., Di Costanzo L, Sabio G, Mora A, Rodriguez PC, Ochoa AC, Centeno F, Christianson DW, Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13058-63. Epub 2005 Sep 2. PMID:16141327

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