View source for 2aeb

[[Image:2aeb.gif|left|200px]]

 {{Structure
|PDB= 2aeb |SIZE=350|CAPTION= <scene name='initialview01'>2aeb</scene>, resolution 1.29&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=AB5:2(S)-AMINO-6-BORONOHEXANOIC+ACID'>AB5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>
|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= 
|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>
}}

'''Crystal structure of human arginase I at 1.29 A resolution and exploration of inhibition in immune response.'''


==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==
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==
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: Homo sapiens]]
[[Category: Single protein]]
[[Category: Centeno, F.]]
[[Category: Christianson, D W.]]
[[Category: Costanzo, L Di.]]
[[Category: Mora, A.]]
[[Category: Ochoa, A C.]]
[[Category: Rodriguez, P C.]]
[[Category: Sabio, G.]]
[[Category: binuclear manganese cluster]]
[[Category: boronic acid inhibitor]]
[[Category: hydrolase]]
[[Category: perfectly twinned crystal]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:51:27 2008''