TY - JOUR
T1 - Structural models for the complex of chemotaxis inhibitory protein of Staphylococcus aureus with the C5a receptor
AU - Nikiforovich, Gregory V.
AU - Baranski, Thomas J.
PY - 2009/12/18
Y1 - 2009/12/18
N2 - The study presents structural models for the complex of the chemotaxis inhibitory protein of Staphylococcus aureus, CHIPS, and receptor for anaphylotoxin C5a, C5aR. The models are based on the recently found NMR structure of the complex between CHIPS fragment 31-121 and C5aR fragment 7-28, as well as on previous results of molecular modeling of C5aR. Simple and straightforward modeling procedure selected low-energy conformations of the C5aR fragment 8-41 that simultaneously fit the NMR structure of the C5aR 10-18 fragment and properly orient the NMR structure of CHIPS31-121 relative to C5aR. Extensive repacking of the side chains of CHIPS31-121 and C5aR8-41 predicted specific residue-residue interactions on the interface between CHIPS and C5aR. Many of these interactions were rationalized with experimental data obtained by site-directed mutagenesis of CHIPS and C5aR. The models correctly showed that CHIPS binds only to the first binding site of C5a to C5aR not competing with C5a fragment 59-74, which binds the second binding site of C5aR. The models also predict that two elements of CHIPS, fragments 48-58 and 97-111, may be used as structural templates for potential inhibitors of C5a.
AB - The study presents structural models for the complex of the chemotaxis inhibitory protein of Staphylococcus aureus, CHIPS, and receptor for anaphylotoxin C5a, C5aR. The models are based on the recently found NMR structure of the complex between CHIPS fragment 31-121 and C5aR fragment 7-28, as well as on previous results of molecular modeling of C5aR. Simple and straightforward modeling procedure selected low-energy conformations of the C5aR fragment 8-41 that simultaneously fit the NMR structure of the C5aR 10-18 fragment and properly orient the NMR structure of CHIPS31-121 relative to C5aR. Extensive repacking of the side chains of CHIPS31-121 and C5aR8-41 predicted specific residue-residue interactions on the interface between CHIPS and C5aR. Many of these interactions were rationalized with experimental data obtained by site-directed mutagenesis of CHIPS and C5aR. The models correctly showed that CHIPS binds only to the first binding site of C5a to C5aR not competing with C5a fragment 59-74, which binds the second binding site of C5aR. The models also predict that two elements of CHIPS, fragments 48-58 and 97-111, may be used as structural templates for potential inhibitors of C5a.
KW - C5a receptor
KW - Chemotaxis inhibitory protein
KW - GPCRs
KW - Molecular modeling
UR - http://www.scopus.com/inward/record.url?scp=70449701449&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.09.113
DO - 10.1016/j.bbrc.2009.09.113
M3 - Article
C2 - 19799858
AN - SCOPUS:70449701449
SN - 0006-291X
VL - 390
SP - 481
EP - 484
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -