Journal article
Inhibition of human arginase I by substrate and product analogues
Archives of biochemistry and biophysics, v 496(2), pp 101-108
15 Apr 2010
PMID: 20153713
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Human arginase I is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of
l-arginine to generate
l-ornithine and urea. We demonstrate that
N-hydroxy-
l-arginine (NOHA) binds to this enzyme with
K
d
=
3.6
μM, and nor-
N-hydroxy-
l-arginine (nor-NOHA) binds with
K
d
=
517
nM (surface plasmon resonance) or
K
d
≈
50
nM (isothermal titration calorimetry). Crystals of human arginase I complexed with NOHA and nor-NOHA afford 2.04 and 1.55
Å resolution structures, respectively, which are significantly improved in comparison with previously-determined structures of the corresponding complexes with rat arginase I. Higher resolution structures clarify the binding interactions of the inhibitors. Finally, the crystal structure of the complex with
l-lysine (
K
d
=
13
μM) is reported at 1.90
Å resolution. This structure confirms the importance of hydrogen bond interactions with inhibitor α-carboxylate and α-amino groups as key specificity determinants of amino acid recognition in the arginase active site.
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Details
- Title
- Inhibition of human arginase I by substrate and product analogues
- Creators
- Luigi Di CostanzoMonica Ilies - University of PennsylvaniaKatherine J. Thorn - University of PennsylvaniaDavid W. Christianson - University of PennsylvaniaArgonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Publication Details
- Archives of biochemistry and biophysics, v 496(2), pp 101-108
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemistry
- Web of Science ID
- WOS:000276757900005
- Scopus ID
- 2-s2.0-77951021970
- Other Identifier
- 991020545126904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics