PDBsum entry 1kh2

Ligase

PDB id: 1kh2

Contents

Protein chains

380 a.a. *

Ligands

ATP ×4

Waters ×385

* Residue conservation analysis

PDB id:

1kh2

Name:

Ligase

Title:

Crystal structure of thermus thermophilus hb8 argininosuccinate synthetase in complex with atp

Structure:

Argininosuccinate synthetase. Chain: a, b, c, d. Engineered: yes

Source:

Thermus thermophilus. Organism_taxid: 274. Gene: hb8. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.30Å R-factor: 0.209 R-free: 0.241

Authors:

M.Goto,Y.Nakajima,K.Hirotsu,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

M.Goto et al. (2002). Crystal structure of argininosuccinate synthetase from Thermus thermophilus HB8. Structural basis for the catalytic action. J Biol Chem, 277, 15890-15896. PubMed id: 11844799 DOI: 10.1074/jbc.M112430200

Date:

29-Nov-01 Release date: 03-Apr-02

Protein chains

P59846  (ASSY_THET8) -  Argininosuccinate synthase from Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8)

Seq: 400 a.a.

Struc: 380 a.a.

Enzyme reactions

• Enzyme class: E.C.6.3.4.5 - argininosuccinate synthase.
• Pathway: Urea Cycle and Arginine Biosynthesis
• Reaction: L-citrulline + L-aspartate + ATP = 2-(N(omega)-L-arginino)succinate + AMP + diphosphate + H⁺

L-citrulline (Bound ligand (Het Group name = ATP) corresponds exactly) + L-aspartate + ATP = 2-(N(omega)-L-arginino)succinate + AMP + diphosphate + H(+)

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

reference

DOI no: 10.1074/jbc.M112430200

J Biol Chem 277:15890-15896 (2002)

PubMed id: 11844799

Crystal structure of argininosuccinate synthetase from Thermus thermophilus HB8. Structural basis for the catalytic action.

M.Goto, Y.Nakajima, K.Hirotsu.

ABSTRACT

Argininosuccinate synthetase catalyzes the ATP-dependent condensation of a citrulline with an aspartate to give argininosuccinate. The three-dimensional structures of the enzyme from Thermus thermophilus HB8 in its free form, complexed with intact ATP, and complexed with an ATP analogue (adenylyl imidodiphosphate) and substrate analogues (arginine and succinate) have been determined at 2.3-, 2.3-, and 1.95-A resolution, respectively. The structure is essentially the same as that of the Escherichia coli argininosuccinate synthetase. The small domain has the same fold as that of a new family of "N-type" ATP pyrophosphatases with the P-loop specific for the pyrophosphate of ATP. However, the enzyme shows the P-loop specific for the gamma-phosphate of ATP. The structure of the complex form is quite similar to that of the native one, indicating that no conformational change occurs upon the binding of ATP and the substrate analogues. ATP and the substrate analogues are bound to the active site with their reaction sites close to one another and located in a geometrical orientation favorable to the catalytic action. The reaction mechanism so far proposed seems to be consistent with the locations of ATP and the substrate analogues. The reaction may proceed without the large conformational change of the enzyme proposed for the catalytic process.

Selected figure(s)

Figure 4.
Fig. 4. Schematic diagram showing hydrogen bond and salt bridge interactions of the active site residues in tAsS·AMP-PNP·arginine·succinate. Putative interactions are shown by dotted lines if the acceptor and donor are less than 3.5 Å apart. W indicates a water molecule. AMP-PNP, arginine, and succinate bound to the active site are drawn by thick bonds.

Figure 5.
Fig. 5. Model of ATP, citrulline, and aspartate binding to tAsS. Important short contacts are shown by dotted lines.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 15890-15896) copyright 2002.

Figures were selected by an automated process.