3MDU: The Structure Of N-formimino-l-glutamate Iminohydrolase From Pseudomonas Aeruginosa Complexed With N-guanidino-l-glutamate

Citation:
Abstract
N-Formimino-l-glutamate iminohydrolase (HutF), from Pseudomonas aeruginosa with a locus tag of Pa5106 ( gi|15600299 ), is a member of the amidohydrolase superfamily. This enzyme catalyzes the deamination of N-formimino-l-glutamate to N-formyl-l-glutamate and ammonia in the histidine degradation pathway. The crystal structure of Pa5106 was determined in the presence of the inhibitors N-formimino-l-aspartate and N-guanidino-l-glutaric acid at resolutions of 1.9 and 1.4 A, respectively. The structure of an individual subunit is composed of two domains with the larger domain folding as a distorted (beta/alpha)8-barrel. The (beta/alpha)8-barrel domain is composed of eight beta-strands flanked by 11 alpha-helices, whereas the smaller domain is made up of eight beta-strands. The active site of Pa5106 contains a single zinc atom that is coordinated by His-56, His-58, His-232, and Asp-320. The nucleophilic solvent water molecule coordinates with the zinc atom at a distance of 2.0 A and is hydrogen bonded to Asp-320 and His-269. The alpha-carboxylate groups of both inhibitors are hydrogen bonded to the imidazole moiety of His-206, the hydroxyl group of Tyr-121, and the side chain amide group of Gln-61. The side chain carboxylate groups of the two inhibitors are ion-paired with the guanidino groups of Arg-209 and Arg-82. Computational docking of high-energy tetrahedral intermediate forms of the substrate, N-formimino-l-glutamate, to the three-dimensional structure of Pa5106 suggests that this compound likely undergoes a re-faced nucleophilic attack at the formimino group by the metal-bound hydroxide. A catalytic mechanism of the reaction catalyzed by Pa5106 is proposed.
PDB ID: 3MDUDownload
MMDB ID: 89057
PDB Deposition Date: 2010/3/30
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 1.4  Å
Source Organism:
Similar Structures:
Biological Unit for 3MDU: monomeric; determined by author
Molecular Components in 3MDU
Label Count Molecule
Protein (1 molecule)
1
N-formimino-l-glutamate Iminohydrolase
Molecule annotation
Chemicals (4 molecules)
1
1
2
1
3
2
* Click molecule labels to explore molecular sequence information.

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