PDBsum entry 3lp7

Hydrolase

PDB id: 3lp7

Contents

Protein chain

313 a.a. *

Ligands

HAR ×2

Metals

_MN ×4

Waters ×272

* Residue conservation analysis

PDB id:

3lp7

Name:

Hydrolase

Title:

Crystal structure of human arginase i in complex with inhibitor n(omega)-hydroxy-l-arginine (noha), 2.04a resolution

Structure:

Arginase-1. Chain: a, b. Synonym: type i arginase, liver-type arginase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: arg1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.04Å R-factor: 0.123 R-free: 0.174

Authors:

L.Di Costanzo,D.W.Christianson

Key ref:

L.Di Costanzo et al. (2010). Inhibition of human arginase I by substrate and product analogues. Arch Biochem Biophys, 496, 101-108. PubMed id: 20153713

Date:

04-Feb-10 Release date: 23-Feb-10

Protein chains

P05089  (ARGI1_HUMAN) -  Arginase-1 from Homo sapiens

Seq: 322 a.a.

Struc: 313 a.a.

Enzyme reactions

• Enzyme class: E.C.3.5.3.1 - arginase.
• Pathway: Urea Cycle and Arginine Biosynthesis
• Reaction: L-arginine + H2O = urea + L-ornithine

L-arginine + H2O (Bound ligand (Het Group name = HAR) matches with 92.31% similarity) = urea + L-ornithine

• Cofactor: Mn(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Arch Biochem Biophys 496:101-108 (2010)

PubMed id: 20153713

Inhibition of human arginase I by substrate and product analogues.

L.Di Costanzo, M.Ilies, K.J.Thorn, D.W.Christianson.

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 microM, and nor-N-hydroxy-L-arginine (nor-NOHA) binds with K(d)=517 nM (surface plasmon resonance) or K(d) approximately 50 nM (isothermal titration calorimetry). Crystals of human arginase I complexed with NOHA and nor-NOHA afford 2.04 and 1.55 A 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 microM) is reported at 1.90 A resolution. This structure confirms the importance of hydrogen bond interactions with inhibitor alpha-carboxylate and alpha-amino groups as key specificity determinants of amino acid recognition in the arginase active site.