TY - JOUR
T1 - The lantibiotic nukacin ISK-1 exists in an equilibrium between active and inactive lipid-II binding states
AU - Fujinami, Daisuke
AU - -Mahin, Abdullah Al
AU - Elsayed, Khaled M.
AU - Islam, Mohammad R.
AU - Nagao, Jun ichi
AU - Roy, Urmi
AU - Momin, Sabrina
AU - Zendo, Takeshi
AU - Kohda, Daisuke
AU - Sonomoto, Kenji
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Number JP26292040 to K.S. and JP26119002 to D.K. K.M.E. acknowledges a fellowship from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. The authors acknowledge Mr. Hajime Motomura (Kyushu University) and Drs. Hiraku Oshima and Yuji Sugita (Riken) for their technical advice on molecular dynamics calculation. The authors also acknowledge Dr. Alexandre Bonvin (Utrecht University) for providing instructive technical information and lipid II and non-natural amino acid files for the HADDOCK calculation.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The lantibiotic nukacin ISK-1 exerts antimicrobial activity through binding to lipid II. Here, we perform NMR analyses of the structure of nukacin ISK-1 and the interaction with lipid II. Unexpectedly, nukacin ISK-1 exists in two structural states in aqueous solution, with an interconversion rate on a time scale of seconds. The two structures differ in the relative orientations of the two lanthionine rings, ring A and ring C. Chemical shift perturbation induced by the titration of lipid II reveals that only one state was capable of binding to lipid II. On the molecular surface of the active state, a multiple hydrogen-bonding site formed by amino acid residues in the ring A region is adjacent to a hydrophobic surface formed by residues in the ring C region, and we propose that these sites interact with the pyrophosphate moiety and the isoprene chain of the lipid II molecule, respectively.
AB - The lantibiotic nukacin ISK-1 exerts antimicrobial activity through binding to lipid II. Here, we perform NMR analyses of the structure of nukacin ISK-1 and the interaction with lipid II. Unexpectedly, nukacin ISK-1 exists in two structural states in aqueous solution, with an interconversion rate on a time scale of seconds. The two structures differ in the relative orientations of the two lanthionine rings, ring A and ring C. Chemical shift perturbation induced by the titration of lipid II reveals that only one state was capable of binding to lipid II. On the molecular surface of the active state, a multiple hydrogen-bonding site formed by amino acid residues in the ring A region is adjacent to a hydrophobic surface formed by residues in the ring C region, and we propose that these sites interact with the pyrophosphate moiety and the isoprene chain of the lipid II molecule, respectively.
UR - http://www.scopus.com/inward/record.url?scp=85066908732&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066908732&partnerID=8YFLogxK
U2 - 10.1038/s42003-018-0150-3
DO - 10.1038/s42003-018-0150-3
M3 - Article
C2 - 30272026
AN - SCOPUS:85066908732
SN - 2399-3642
VL - 1
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 150
ER -