2aeb: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2aeb |SIZE=350|CAPTION= <scene name='initialview01'>2aeb</scene>, resolution 1.29Å | |PDB= 2aeb |SIZE=350|CAPTION= <scene name='initialview01'>2aeb</scene>, resolution 1.29Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=AB5:2(S)-AMINO-6-BORONOHEXANOIC+ACID'>AB5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1vwa|1vwa]], [[1d3v|1D3V]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aeb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aeb OCA], [http://www.ebi.ac.uk/pdbsum/2aeb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2aeb RCSB]</span> | |||
}} | }} | ||
| Line 30: | Line 33: | ||
[[Category: Rodriguez, P C.]] | [[Category: Rodriguez, P C.]] | ||
[[Category: Sabio, G.]] | [[Category: Sabio, G.]] | ||
[[Category: binuclear manganese cluster]] | [[Category: binuclear manganese cluster]] | ||
[[Category: boronic acid inhibitor]] | [[Category: boronic acid inhibitor]] | ||
| Line 37: | Line 38: | ||
[[Category: perfectly twinned crystal]] | [[Category: perfectly twinned crystal]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:51:27 2008'' | ||
Revision as of 01:51, 31 March 2008
| |||||||
| , resolution 1.29Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Arginase, with EC number 3.5.3.1 | ||||||
| Related: | 1vwa, 1D3V
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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
Page seeded by OCA on Mon Mar 31 01:51:27 2008