1KKB

Complex of Escherichia coli Adenylosuccinate Synthetase with IMP and Hadacidin

Summary for 1KKB

• Entry DOI: 10.2210/pdb1kkb/pdb
• Related: 1CIB 1KJX
• Descriptor: Adenylosuccinate Synthetase, HADACIDIN, INOSINIC ACID, ... (4 entities in total)
• Functional Keywords: ligase, gtp-hydrolysing enzymes, purine nucleotide, biosynthesis, induced fit
• Biological source: Escherichia coli K12
• Total number of polymer chains: 1
• Total formula weight: 47868.07

Authors

Hou, Z.,Wang, W.,Fromm, H.J.,Honzatko, R.B. (deposition date: 2001-12-06, release date: 2002-03-20, Last modification date: 2024-02-14)

Primary citation

Hou, Z.,Wang, W.,Fromm, H.J.,Honzatko, R.B.
IMP Alone Organizes the Active Site of Adenylosuccinate Synthetase from Escherichia coli.
J.Biol.Chem., 277:5970-5976, 2002

PubMed Abstract: A complete set of substrate/substrate analogs of adenylosuccinate synthetase from Escherichia coli induces dimer formation and a transition from a disordered to an ordered active site. The most striking of the ligand-induced effects is the movement of loop 40-53 by up to 9 A. Crystal structures of the partially ligated synthetase, which either combine IMP and hadacidin or IMP, hadacidin, and Mg(2+)-pyrophosphate, have ordered active sites, comparable with the fully ligated enzyme. More significantly, a crystal structure of the synthetase with IMP alone exhibits a largely ordered active site, which includes the 9 A movement of loop 40-53 but does not include conformational adjustments to backbone carbonyl 40 (Mg(2+) interaction element) and loop 298-304 (L-aspartate binding element). Interactions involving the 5'-phosphoryl group of IMP evidently trigger the formation of salt links some 30 A away. The above provides a structural basis for ligand binding synergism, effects on k(cat) due to mutations far from the site of catalysis, and the complete loss of substrate efficacy due to minor alterations of the 5'-phosphoryl group of IMP.

PubMed: 11741996
DOI: 10.1074/jbc.M109561200

Experimental method

X-RAY DIFFRACTION (2.6 Å)