4OSX

STRUCTURE of UNCLEAVED GLYCINE-BOUND HUMAN L-ASPARAGINASE PROTEIN

Replaces:  4HLO

Summary for 4OSX

• Entry DOI: 10.2210/pdb4osx/pdb
• Related: 4OSY
• Descriptor: Isoaspartyl peptidase/L-asparaginase, SODIUM ION, GLYCINE, ... (4 entities in total)
• Functional Keywords: ntn enzyme, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q7L266
• Total number of polymer chains: 2
• Total formula weight: 64886.59

Authors

Nomme, J.,Lavie, A. (deposition date: 2014-02-13, release date: 2014-03-05, Last modification date: 2023-09-20)

Primary citation

Su, Y.,Karamitros, C.S.,Nomme, J.,Mcsorley, T.,Konrad, M.,Lavie, A.
Free Glycine Accelerates the Autoproteolytic Activation of Human Asparaginase.
Chem.Biol., 20:533-, 2013

PubMed Abstract: 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.

PubMed: 23601642
DOI: 10.1016/J.CHEMBIOL.2013.03.006

Experimental method

X-RAY DIFFRACTION (1.95 Å)