8HX8

Crystal structure of 4-amino-4-deoxychorismate synthase from Streptomyces venezuelae co-crystallized with chorismate

Summary for 8HX8

• Entry DOI: 10.2210/pdb8hx8/pdb
• Related: 8HX6 8HX7
• Descriptor: 4-amino-4-deoxychorismate synthase, TRYPTOPHAN, SUCCINIC ACID, ... (5 entities in total)
• Functional Keywords: synthase, multi-domain, chorismate, transferase
• Biological source: Streptomyces venezuelae
• Total number of polymer chains: 2
• Total formula weight: 154063.85

Authors

Nakamichi, Y.,Watanabe, M. (deposition date: 2023-01-04, release date: 2023-10-18, Last modification date: 2023-11-15)

Primary citation

Nakamichi, Y.,Kobayashi, J.,Toyoda, K.,Suda, M.,Hiraga, K.,Inui, M.,Watanabe, M.
Structural basis for the allosteric pathway of 4-amino-4-deoxychorismate synthase.
Acta Crystallogr D Struct Biol, 79:895-908, 2023

PubMed Abstract: 4-Amino-4-deoxychorismate synthase (ADCS), a chorismate-utilizing enzyme, is composed of two subunits: PabA and PabB. PabA is a glutamine amidotransferase that hydrolyzes glutamine into glutamate and ammonia. PabB is an aminodeoxychorismate synthase that converts chorismate to 4-amino-4-deoxychorismate (ADC) using the ammonia produced by PabA. ADCS functions under allosteric regulation between PabA and PabB. However, the allosteric mechanism remains unresolved because the structure of the PabA-PabB complex has not been determined. Here, the crystal structure and characterization of PapA from Streptomyces venezuelae (SvPapA), a bifunctional enzyme comprising the PabA and PabB domains, is reported. SvPapA forms a unique dimer in which PabA and PabB domains from different monomers complement each other and form an active structure. The chorismate-bound structure revealed that recognition of the C1 carboxyl group by Thr501 and Gly502 of the 498-PIKTG-502 motif in the PabB domain is essential for the catalytic Lys500 to reach the C2 atom, a reaction-initiation site. SvPapA demonstrated ADCS activity in the presence of Mg when glutamate or NH was used as the amino donor. The crystal structure indicated that the Mg-binding position changed depending on the binding of chorismate. In addition, significant structural changes were observed in the PabA domain depending on the presence or absence of chorismate. This study provides insights into the structural factors that are involved in the allosteric regulation of ADCS.

PubMed: 37712435
DOI: 10.1107/S2059798323006320

Experimental method

X-RAY DIFFRACTION (2.55 Å)