TY - JOUR
T1 - Crystal structure of EstSRT1, a family VIII carboxylesterase displaying hydrolytic activity toward oxyimino cephalosporins
AU - Cha, Sun Shin
AU - An, Young Jun
N1 - Funding Information:
We thank Sung Gyun Kang for providing the EstSRT1 clone and KyoungWoo Park for assistance with figure preparation. This study was supported by National Research Foundation of Korea Grants (NRF- 2015R1A2A2A01004168 and NRF- 2015M1A5A1037480 ) and the KIOST in-house program ( PE99413 ).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/9/16
Y1 - 2016/9/16
N2 - EstSRT1 is a family VIII carboxylesterase that hydrolyzes oxyimino third- and fourth-generation cephalosporins, first-generation cephalosporins and ester substrates. According to the crystal structure of EstSRT1 (2.0-Å resolution), this protein contains a large α/β domain and a small α-helical domain and harbors three catalytic residues (Ser71, Lys74, and Tyr160) in the cavity at the domain interface, similarly to other family VIII carboxylesterases. Comparison of the structures of EstSRT1 and EstU1, a family VIII carboxylesterase with no hydrolytic activity toward bulky oxyimino cephalosporins, revealed that EstSRT1 has a smaller active site, despite its extended substrate range. The B-factors of the active site segments that could potentially contact with the oxyimino groups and the R2 side chains of oxyimino cephalosporins are higher in EstSRT1 than in EstU1, thus suggesting the role of the active site's structural flexibility in the extension of EstSRT1's substrate spectrum.
AB - EstSRT1 is a family VIII carboxylesterase that hydrolyzes oxyimino third- and fourth-generation cephalosporins, first-generation cephalosporins and ester substrates. According to the crystal structure of EstSRT1 (2.0-Å resolution), this protein contains a large α/β domain and a small α-helical domain and harbors three catalytic residues (Ser71, Lys74, and Tyr160) in the cavity at the domain interface, similarly to other family VIII carboxylesterases. Comparison of the structures of EstSRT1 and EstU1, a family VIII carboxylesterase with no hydrolytic activity toward bulky oxyimino cephalosporins, revealed that EstSRT1 has a smaller active site, despite its extended substrate range. The B-factors of the active site segments that could potentially contact with the oxyimino groups and the R2 side chains of oxyimino cephalosporins are higher in EstSRT1 than in EstU1, thus suggesting the role of the active site's structural flexibility in the extension of EstSRT1's substrate spectrum.
KW - Crystal structure
KW - EstSRT1
KW - Extended hydrolytic activity toward oxyimino cephalosporins
KW - Family VIII carboxylesterases
KW - Flexibility of the active site
UR - http://www.scopus.com/inward/record.url?scp=84995489844&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2016.08.031
DO - 10.1016/j.bbrc.2016.08.031
M3 - Article
C2 - 27501751
AN - SCOPUS:84995489844
SN - 0006-291X
VL - 478
SP - 818
EP - 824
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -