PDBsum entry: 2nz2

Ligase

PDB id: 2nz2

Contents

Protein chain

402 a.a. *

Ligands

ASP

CIR

Metals

_NA

Waters ×210

* Residue conservation analysis

PDB id:

2nz2

Name:

Ligase

Title:

Crystal structure of human argininosuccinate synthase in com aspartate and citrulline

Structure:

Argininosuccinate synthase. Chain: a. Synonym: citrulline--aspartate ligase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ass1, ass. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.40Å R-factor: 0.198 R-free: 0.265

Authors:

T.Karlberg,J.Uppenberg,C.Arrowsmith,H.Berglund,R.D.Busam,R.C A.Edwards,U.B.Ericsson,S.Flodin,A.Flores,S.Graslund,B.M.Hal M.Hammarstrom,M.Hogbom,I.Johansson,T.Kotenyova,A.Magnusdott M.Moche,M.E.Nilsson,P.Nordlund,T.Nyman,D.Ogg,C.Persson,J.Sa P.Stenmark,M.Sundstrom,A.G.Thorsell,S.Van Den Berg,K.Wallde J.Weigelt,L.Holmberg-Schiavone,Structural Genomics Consorti

Key ref:

T.Karlberg et al. (2008). Structure of human argininosuccinate synthetase. Acta Crystallogr D Biol Crystallogr, 64, 279-286. PubMed id: 18323623 DOI: 10.1107/S0907444907067455

Date:

22-Nov-06 Release date: 05-Dec-06

Protein chain

P00966  (ASSY_HUMAN) -  Argininosuccinate synthase

Seq: 412 a.a.

Struc: 402 a.a.

Enzyme reactions

• Enzyme class: E.C.6.3.4.5 - Argininosuccinate synthase.
• Pathway: Urea Cycle and Arginine Biosynthesis
• Reaction: ATP + L-citrulline + L-aspartate = AMP + diphosphate + N(omega)- (L-arginino)succinate

ATP + L-citrulline (Bound ligand (Het Group name = CIR) corresponds exactly) + L-aspartate (Bound ligand (Het Group name = ASP) corresponds exactly) = AMP + diphosphate + N(omega)- (L-arginino)succinate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cell body fiber (11 terms)
• Biological process: cellular response to lipopolysaccharide (36 terms)
• Biochemical function: nucleotide binding (6 terms)

reference

DOI no: 10.1107/S0907444907067455

Acta Crystallogr D Biol Crystallogr 64:279-286 (2008)

PubMed id: 18323623

Structure of human argininosuccinate synthetase.

T.Karlberg, R.Collins, S.van den Berg, A.Flores, M.Hammarström, M.Högbom, L.Holmberg Schiavone, J.Uppenberg.

ABSTRACT

Argininosuccinate synthetase catalyzes the transformation of citrulline and aspartate into argininosuccinate and pyrophosphate using the hydrolysis of ATP to AMP and pyrophosphate. This enzymatic process constitutes the rate-limiting step in both the urea and arginine-citrulline cycles. Previous studies have investigated the crystal structures of argininosuccinate synthetase from bacterial species. In this work, the first crystal structure of human argininosuccinate synthetase in complex with the substrates citrulline and aspartate is presented. The human enzyme is compared with structures of argininosuccinate synthetase from bacteria. In addition, the structure also provides new insights into the function of the numerous clinical mutations identified in patients with type I citrullinaemia (also known as classic citrullinaemia).

Selected figure(s)

Figure 2.
Figure 2 The substrates citrulline and aspartate modelled into the electron density. Human argininosuccinate synthetase (hASS) was cocrystallized with the two substrate molecules citrulline and aspartate. [A]-weighted 2F[obs] - F[calc] density at 2.4 Å resolution is shown for these ligands. The ligand-protein interactions for hASS closely resemble those reported previously for bacterial structures. All figures were produced using PyMOL (DeLano, 2002[DeLano, W. L. (2002). The PyMOL User's Manual. DeLano Scientific, San Carlos, USA.]).

Figure 4.
Figure 4 Cys132 and nitrosylation. The side chain of Cys132 is nitrosylated by nitric oxide synthase (NOS) as a down-regulating feedback mechanism (Hao et al., 2004[Hao, G., Xie, L. & Gross, S. S. (2004). J. Biol. Chem. 279, 36192-36200.]). NOS and argininosuccinate synthetase belong to the same pathway, the arginine-citrulline cycle. (a) In the nonnitrosylated structure of human ASS, the cysteine side chain is not located in the immediate vicinity of the active site. A small cavity, here shown as a van der Waals surface, is found next to the side-chain sulfur. (b) A group of nitrosylated cysteine residues found on proteins in the Protein Data Bank have been superimposed with Cys132.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2008, 64, 279-286) copyright 2008.

Figures were selected by the author.