3NYE

Crystal Structure of Pseudomonas aeruginosa D-Arginine Dehydrogenase in Complex with Imino-Arginine

Summary for 3NYE

• Entry DOI: 10.2210/pdb3nye/pdb
• Related: 3NYC 3NYF
• Descriptor: D-Arginine Dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE, (2E)-5-[(diaminomethylidene)amino]-2-iminopentanoic acid, ... (4 entities in total)
• Functional Keywords: d-arginine dehydrogenase, fad, imino-arginine, oxidoreductase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 42363.24

Authors

Fu, G.,Weber, I.T. (deposition date: 2010-07-14, release date: 2010-09-15, Last modification date: 2023-09-06)

Primary citation

Fu, G.,Yuan, H.,Li, C.,Lu, C.D.,Gadda, G.,Weber, I.T.
Conformational changes and substrate recognition in Pseudomonas aeruginosa D-arginine dehydrogenase.
Biochemistry, 49:8535-8545, 2010

PubMed Abstract: DADH catalyzes the flavin-dependent oxidative deamination of d-amino acids to the corresponding α-keto acids and ammonia. Here we report the first X-ray crystal structures of DADH at 1.06 Å resolution and its complexes with iminoarginine (DADH(red)/iminoarginine) and iminohistidine (DADH(red)/iminohistidine) at 1.30 Å resolution. The DADH crystal structure comprises an unliganded conformation and a product-bound conformation, which is almost identical to the DADH(red)/iminoarginine crystal structure. The active site of DADH was partially occupied with iminoarginine product (30% occupancy) that interacts with Tyr53 in the minor conformation of a surface loop. This flexible loop forms an "active site lid", similar to those seen in other enzymes, and may play an essential role in substrate recognition. The guanidinium side chain of iminoarginine forms a hydrogen bond interaction with the hydroxyl of Thr50 and an ionic interaction with Glu87. In the structure of DADH in complex with iminohistidine, two alternate conformations were observed for iminohistidine where the imidazole groups formed hydrogen bond interactions with the side chains of His48 and Thr50 and either Glu87 or Gln336. The different interactions and very distinct binding modes observed for iminoarginine and iminohistidine are consistent with the 1000-fold difference in k(cat)/K(m) values for d-arginine and d-histidine. Comparison of the kinetic data for the activity of DADH on different d-amino acids and the crystal structures in complex with iminoarginine and iminohistidine establishes that this enzyme is characterized by relatively broad substrate specificity, being able to oxidize positively charged and large hydrophobic d-amino acids bound within a flask-like cavity.

PubMed: 20809650
DOI: 10.1021/bi1005865

Experimental method

X-RAY DIFFRACTION (1.3 Å)