2aeb: Difference between revisions
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'''Crystal structure of human arginase I at 1.29 A resolution and exploration of inhibition in immune response.''' | {{Structure | ||
|PDB= 2aeb |SIZE=350|CAPTION= <scene name='initialview01'>2aeb</scene>, resolution 1.29Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> and <scene name='pdbligand=AB5:2(S)-AMINO-6-BORONOHEXANOIC ACID'>AB5</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 human arginase I at 1.29 A resolution and exploration of inhibition in immune response.''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2AEB is a [ | 2AEB 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=2AEB OCA]. | ||
==Reference== | ==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:[http:// | 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: perfectly twinned crystal]] | [[Category: perfectly twinned crystal]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:48:37 2008'' | ||
Revision as of 16:48, 20 March 2008
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| , resolution 1.29Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Arginase, with EC number 3.5.3.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human arginase I at 1.29 A resolution and exploration of inhibition in immune response.
OverviewOverview
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 StructureAbout this Structure
2AEB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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