4OSY: Structure Of Fully-cleaved Glycine-bound Human L-asparaginase Protein

Human asparaginase 3 (hASNase3), which belongs to the N-terminal nucleophile hydrolase superfamily, is synthesized as a single polypeptide that is devoid of asparaginase activity. Intramolecular autoproteolytic processing releases the amino group of Thr168, a moiety required for catalyzing asparagine hydrolysis. Recombinant hASNase3 purifies as the uncleaved, asparaginase-inactive form and undergoes self-cleavage to the active form at a very slow rate. Here, we show that the free amino acid glycine selectively acts to accelerate hASNase3 cleavage both in vitro and in human cells. Other small amino acids such as alanine, serine, or the substrate asparagine are not capable of promoting autoproteolysis. Crystal structures of hASNase3 in complex with glycine in the uncleaved and cleaved enzyme states reveal the mechanism of glycine-accelerated posttranslational processing and explain why no other amino acid can substitute for glycine.
PDB ID: 4OSYDownload
MMDB ID: 118124
PDB Deposition Date: 2014/2/13
Updated in MMDB: 2014/03
Experimental Method:
x-ray diffraction
Resolution: 1.91  Å
Source Organism:
Similar Structures:
Biological Unit for 4OSY: dimeric; determined by author and by software (PISA)
Molecular Components in 4OSY
Label Count Molecule
Proteins (2 molecules)
Isoaspartyl Peptidase/l-asparaginase(Gene symbol: ASRGL1)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB