PDBsum entry 1hg0

Asparaginase

PDB id: 1hg0

Contents

Protein chains

327 a.a. *

Ligands

SIN ×4

Waters ×881

* Residue conservation analysis

PDB id:

1hg0

Name:

Asparaginase

Title:

X-ray structure of the complex between erwinia chrysanthemi l- asparaginase and succinic acid

Structure:

L-asparaginase. Chain: a, b, c, d. Synonym: l-asparagine amidohydrolase, l-asnase. Ec: 3.5.1.1

Source:

Erwinia chrysanthemi. Organism_taxid: 556. Strain: ncppb 1125. Other_details: the new name of erwinia chrysanthemi is pectobacterium chrysanthemi

Biol. unit:

Tetramer (from PQS)

Resolution:

1.90Å R-factor: 0.171 R-free: 0.199

Authors:

J.Lubkowski,A.Wlodawer,K.A.Kolyani

Key ref:

K.Aghaiypour et al. (2001). Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase. Biochemistry, 40, 5655-5664. PubMed id: 11341830 DOI: 10.1021/bi0029595

Date:

08-Dec-00 Release date: 07-Aug-01

Protein chains

P06608  (ASPG_DICCH) -  L-asparaginase from Dickeya chrysanthemi

Seq: 348 a.a.

Struc: 327 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.5.1.1 - asparaginase.
• Reaction: L-asparagine + H2O = L-aspartate + NH4⁺

L-asparagine + H2O = L-aspartate (Bound ligand (Het Group name = SIN) matches with 88.89% similarity) + NH4(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/bi0029595

Biochemistry 40:5655-5664 (2001)

PubMed id: 11341830

Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase.

K.Aghaiypour, A.Wlodawer, J.Lubkowski.

ABSTRACT

Bacterial L-asparaginases, enzymes that catalyze the hydrolysis of L-asparagine to aspartic acid, have been used for over 30 years as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia. Other substrates of asparaginases include L-glutamine, D-asparagine, and succinic acid monoamide. In this report, we present high-resolution crystal structures of the complexes of Erwinia chrysanthemi L-asparaginase (ErA) with the products of such reactions that also can serve as substrates, namely L-glutamic acid (L-Glu), D-aspartic acid (D-Asp), and succinic acid (Suc). Comparison of the four independent active sites within each complex indicates unique and specific binding of the ligand molecules; the mode of binding is also similar between complexes. The lack of the alpha-NH3(+) group in Suc, compared to L-Asp, does not affect the binding mode. The side chain of L-Glu, larger than that of L-Asp, causes several structural distortions in the ErA active side. The active site flexible loop (residues 15-33) does not exhibit stable conformation, resulting in suboptimal orientation of the nucleophile, Thr15. Additionally, the delta-COO(-) plane of L-Glu is approximately perpendicular to the plane of gamma-COO(-) in L-Asp bound to the asparaginase active site. Binding of D-Asp to the ErA active site is very distinctive compared to the other ligands, suggesting that the low activity of ErA against D-Asp could be mainly attributed to the low k(cat) value. A comparison of the amino acid sequence and the crystal structure of ErA with those of other bacterial L-asparaginases shows that the presence of two active-site residues, Glu63(ErA) and Ser254(ErA), may correlate with significant glutaminase activity, while their substitution by Gln and Asn, respectively, may lead to minimal L-glutaminase activity.