@article{488679af7163402ca58e1724358b4867,
title = "Structural basis of the cooperative activation of type II citrate synthase (HyCS) from Hymenobacter sp. PAMC 26554",
abstract = "Citrate synthase (CS) catalyzes the formation of citrate and coenzyme A from acetyl-CoA and oxaloacetate. CS exists in two forms: type I and type II. We determined the citrate-bound crystal structure of type II CS from the Hymenobacter sp. PAMC 26554 bacterium (HyCS; isolated from Antarctic lichen). Citrate molecules bound to a cleft between the large and small domains of HyCS. Structural comparison of HyCS with other type II CSs revealed that type II CSs have a highly conserved flexible hinge region (residues G264–P265 in HyCS), enabling correct positioning of active site residues. Notably, the catalytic His266 residue of HyCS interacted with Trp262 in the inactive (unliganded open) state of other type II CSs, whereas the His266 residue moved to the active site via a small-domain swing motion, interacting with the bound citrate in the closed conformation of HyCS. However, type I CSs lack this tryptophan residue and face-to-edge interactions. Thus, type II CSs might have a unique domain-motion control mechanism enabling a tight allosteric regulation. An activity assay using a W262A mutant showed a Hill coefficient of 2.4; thus, the interaction between Trp262 and His266 was closely related to the positive cooperative ligand binding of type II CS.",
keywords = "Citrate synthase, Crystal structure, Domain movement, Hymenobacter sp. PAMC 26554, X-ray crystallography",
author = "Park, {Sun Ha} and Lee, {Chang Woo} and Bae, {Da Woon} and Hackwon Do and Jeong, {Chang Sook} and Jisub Hwang and Cha, {Sun Shin} and Lee, {Jun Hyuck}",
note = "Funding Information: We thank the staff at the X-ray core facility of the Korea Basic Science Institute (Ochang, Korea) and BL-5C of the Pohang Accelerator Laboratory (Pohang, Korea) for their assistance with data collection. This research was a part of the project titled “Development of potential antibiotic compounds using polar organism resources (15250103, KOPRI Grant PM21030)” funded by the Ministry of Oceans and Fisheries, Korea. This research was also supported by a National Research Foundation of Korea Grant from the Korean Government (MSIT; the Ministry of Science and ICT) (NRF-2017M1A5A1013568) (KOPRI-PN20082) (Title: Application study on the Arctic cold-active enzyme degrading organic carbon compounds). Atomic coordinates and structure factors for the citrate-bound HyCS structure were deposited in the PDB under accession code 7E8N. Funding Information: We thank the staff at the X-ray core facility of the Korea Basic Science Institute (Ochang, Korea) and BL-5C of the Pohang Accelerator Laboratory (Pohang, Korea) for their assistance with data collection. This research was a part of the project titled “Development of potential antibiotic compounds using polar organism resources (15250103, KOPRI Grant PM21030)” funded by the Ministry of Oceans and Fisheries, Korea. This research was also supported by a National Research Foundation of Korea Grant from the Korean Government (MSIT; the Ministry of Science and ICT) ( NRF-2017M1A5A1013568 ) ( KOPRI-PN20082 ) (Title: Application study on the Arctic cold-active enzyme degrading organic carbon compounds). Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = jul,
day = "31",
doi = "10.1016/j.ijbiomac.2021.04.141",
language = "English",
volume = "183",
pages = "213--221",
journal = "International Journal of Biological Macromolecules",
issn = "0141-8130",
publisher = "Elsevier",
}