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정창숙Chang-Sook Jeong

극지연구소, 현 에피노젠

Int. J. Antimicrob. Agents, Apr 06 2024, S0924-8579(24)00089-X | https://doi.org/10.1016/j.ijantimicag.2024.107171 Characterization of the extended substrate spectrum of the class A β-lactamase CESS-1 from Stenotrophomonas sp. and structure-based investigation into its substrate preference

Bo-Gyeong Jeong ^a,1, Myeong-Yeon Kim ^a,1, Chang-Sook Jeong ^b,c,1, Hackwon Do ^b,c, Jisub Hwang ^b,c, Jun Hyuck Lee ^b,c, Sun-Shin Cha^a

^aDepartment of Chemistry & Nanoscience, Ewha Womans University, Seoul, 03760, Republic of Korea

^bResearch Unit of Cryogenic Novel Material, Korea Polar Research Institute, Incheon, 21990, Republic of Korea

^cDepartment of Polar Sciences, University of Science and Technology, Incheon, 21990, Republic of Korea

¹These authors contributed equally to this work.

Correspondence: Jun Hyuck Lee, Sun-Shin Cha

Abstract

Stenotrophomonas spp. intrinsically resistant to many β-lactam antibiotics are found throughout the environment. CESS-1 identified in Stenotrophomonas sp. KCTC 12332 is an uncharacterized class A β-lactamase. Here, CESS-1 was revealed to display hydrolytic activities toward penicillins (penicillin G and ampicillin) and cephalosporins (cephalexin, cefaclor, and cefotaxime), while its activity toward carbapenems (imipenem and meropenem) was negligible. Although cefaclor, cephalexin, and ampicillin have similar structures with identical R1 side chains, the catalytic parameters of CESS-1 toward the three β-lactam antibiotics were distinct. The k _cat values for cefaclor, cephalexin, and ampicillin were calculated to be 1249.6 s ^-1, 204.3 s ^-1, and 69.8 s ^-1, respectively, with the accompanying K _M values of 287.6 μM, 236.7 μM, and 28.8 μM, respectively. Remarkably, CESS-1 discriminates cefaclor and cephalexin with only one structural difference: -Cl (cefaclor) and -CH ₃ (cephalexin) at C3. According to structural comparisons among three E166Q mutants of CESS-1 acylated by cefaclor, cephalexin, and ampicillin, the cooperative positional changes of the R1 side chain of substrates and its contacting β5-β6 loop affect the distance between Asn170 and the deacylating water at the acyl-enzyme intermediate state. This is directly associated with the differential hydrolytic activities of CESS-1 toward the three structurally similar β-lactam antibiotics.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-09)
연구진국내 연구진
분야 생명과학 > 구조생물 및 생물물리학

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