4M8D: Crystal structure of an isatin hydrolase bound to product analogue thioisatinate

The high resolution crystal structures of isatin hydrolase from Labrenzia aggregata in the apo and the product state are described. These are the first structures of a functionally characterized metal-dependent hydrolase of this fold. Isatin hydrolase converts isatin to isatinate and belongs to a novel family of metalloenzymes that include the bacterial kynurenine formamidase. The product state, mimicked by bound thioisatinate, reveals a water molecule that bridges the thioisatinate to a proton wire in an adjacent water channel and thus allows the proton released by the reaction to escape only when the product is formed. The functional proton wire present in isatin hydrolase isoform b represents a unique catalytic feature common to all hydrolases is here trapped and visualized for the first time. The local molecular environment required to coordinate thioisatinate allows stronger and more confident identification of orthologous genes encoding isatin hydrolases within the prokaryotic kingdom. The isatin hydrolase orthologues found in human gut bacteria raise the question as to whether the indole-3-acetic acid degradation pathway is present in human gut flora.
PDB ID: 4M8DDownload
MMDB ID: 120786
PDB Deposition Date: 2013/8/13
Updated in MMDB: 2014/08
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Similar Structures:
Biological Unit for 4M8D: dimeric; determined by author and by software (PISA)
Molecular Components in 4M8D
Label Count Molecule
Proteins (2 molecules)
Putative Uncharacterized Protein
Molecule annotation
Chemicals (9 molecules)
* Click molecule labels to explore molecular sequence information.

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