PDBsum entry: 2dgn

Ligase

PDB id: 2dgn

Contents

Protein chain

431 a.a. *

Ligands

DOI

GDP

Metals

_MG

Waters ×127

* Residue conservation analysis

PDB id:

2dgn

Name:

Ligase

Title:

Mouse muscle adenylosuccinate synthetase partially ligated c with gtp, 2'-deoxy-imp

Structure:

Adenylosuccinate synthetase isozyme 1. Chain: a. Synonym: adenylosuccinate synthetase, muscle isozyme, imp-- ligase 1, adss 1, ampsase 1. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.40Å R-factor: 0.198 R-free: 0.262

Authors:

C.V.Iancu,Y.Zhou,T.Borza,H.J.Fromm,R.B.Honzatko

Key ref:

C.V.Iancu et al. (2006). Cavitation as a mechanism of substrate discrimination by adenylosuccinate synthetases. Biochemistry, 45, 11703-11711. PubMed id: 16981730 DOI: 10.1021/bi0607498

Date:

15-Mar-06 Release date: 15-Sep-06

Protein chain

P28650  (PURA1_MOUSE) -  Adenylosuccinate synthetase isozyme 1

Seq: 457 a.a.

Struc: 431 a.a.

Enzyme reactions

• Enzyme class: E.C.6.3.4.4 - Adenylosuccinate synthase.
• Pathway: AMP and GMP Biosynthesis
• Reaction: GTP + IMP + L-aspartate = GDP + phosphate + N₆-(1,2-dicarboxyethyl)- AMP

GTP + IMP + L-aspartate = GDP (Bound ligand (Het Group name = GDP) corresponds exactly) + phosphate + N(6)-(1,2-dicarboxyethyl)- AMP

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

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (2 terms)
• Biological process: purine nucleotide metabolic process (2 terms)
• Biochemical function: nucleotide binding (7 terms)

reference

DOI no: 10.1021/bi0607498

Biochemistry 45:11703-11711 (2006)

PubMed id: 16981730

Cavitation as a mechanism of substrate discrimination by adenylosuccinate synthetases.

C.V.Iancu, Y.Zhou, T.Borza, H.J.Fromm, R.B.Honzatko.

ABSTRACT

Adenylosuccinate synthetase catalyzes the first committed step in the de novo biosynthesis of AMP, coupling L-aspartate and IMP to form adenylosuccinate. Km values of IMP and 2'-deoxy-IMP are nearly identical with each substrate supporting comparable maximal velocities. Nonetheless, the Km value for L-aspartate and the Ki value for hadacidin (a competitive inhibitor with respect to L-aspartate) are 29-57-fold lower in the presence of IMP than in the presence of 2'-deoxy-IMP. Crystal structures of the synthetase ligated with hadacidin, GDP, and either 6-phosphoryl-IMP or 2'-deoxy-6-phosphoryl-IMP are identical except for the presence of a cavity normally occupied by the 2'-hydroxyl group of IMP. In the presence of 6-phosphoryl-IMP and GDP (hadacidin absent), the L-aspartate pocket can retain its fully ligated conformation, forming hydrogen bonds between the 2'-hydroxyl group of IMP and sequence-invariant residues. In the presence of 2'-deoxy-6-phosphoryl-IMP and GDP, however, the L-aspartate pocket is poorly ordered. The absence of the 2'-hydroxyl group of the deoxyribonucleotide may destabilize binding of the ligand to the L-aspartate pocket by disrupting hydrogen bonds that maintain a favorable protein conformation and by the introduction of a cavity into the fully ligated active site. At an approximate energy cost of 2.2 kcal/mol, the unfavorable thermodynamics of cavity formation may be the major factor in destabilizing ligands at the L-aspartate pocket.