Crystal structure of SMU.2055 protein fromStreptococcus mutans and its small molecule inhibitors design and selec- tion
10.7518/hxkq.2015.02.016
- VernacularTitle:变异链球菌SMU.2055蛋白晶体结构及其小分子抑制剂设计与筛选
- Author:
Xiaodan CHEN
1
;
Xiurong ZHAN
;
Xinyu WU
;
Chunyan ZHAO
;
Wanghong ZHAO
Author Information
1. 南方医科大学南方医院口腔科
- Keywords:
Streptococcus mutans;
protein crystallo-graphy;
small molecule inhibitors
- From:
West China Journal of Stomatology
2015;(2):182-186
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThe?aim?of?this?study?is?to?analyze?the?three-dimensional?crystal?structure?of?SMU.2055?protein,?a?putative?acetyltransferase?from?the?major?caries?pathogen?Streptococcus mutans(S.mutans).?The?design?and?selection?of?the?structure-based?small?molecule?inhibitors?are?also?studied.?Methods???The?three-dimensional?crystal?structure?of?SMU.2055?protein?was?obtained?by?structural?genomics?research?methods?of?gene?cloning?and?expression,?protein?purification?with?Ni2+-chelating?affinity?chromatography,?crystal?screening,?and?X-ray?diffraction?data?collection.?An?inhibitor?virtual?model?matching?with?its?target?protein?structure?was?set?up?using?computer-aided?drug?design?methods,?virtual?screening?and?fine?docking,?and?Libdock?and?Autodock?procedures.?Results???The?crystal?of?SMU.2055?protein?was?obtained,?and?its?three-dimensional?crystal?structure?was?analyzed.?This?crystal?was?diffracted?to?a?resolution?of?0.23?nm.?It?belongs?to?orthorhombic?space?group?C2221,?with unit cell parameters of a=9.20nm, b=9.46nm, and c=19.39nm. The asymmetric unit contained four molecules, with a solvent?content?of?56.7%.?Moreover,?five?small?molecule?compounds,?whose?structure?matched?with?that?of?the?target?protein?in?high?degree,?were?designed?and?selected.?Conclusion???Protein?crystallography?research?of?S. mutans?SMU.2055?helps?to?under-stand?the?structures?and?functions?of?proteins?from?S. mutans?at?the?atomic?level.?These?five?compounds?may?be?considered?as?effec-tive?inhibitors?to?SMU.2055.?The?virtual?model?of?small?mole-cule?inhibitors?we?built?will?lay?a?foundation?to?the?anticaries?research?based?on?the?crystal?structure?of?proteins.
