中华传染病杂志
中華傳染病雜誌
중화전염병잡지
CHINESE JOURNAL OF INFECTIOUS DISEASES
2013年
4期
208-211
,共4页
克雷伯菌,肺炎%DNA拓扑异构酶类,Ⅱ型%喹诺酮类%变异(遗传学)%分子构象%蛋白质结合%药物耐受性
剋雷伯菌,肺炎%DNA拓撲異構酶類,Ⅱ型%喹諾酮類%變異(遺傳學)%分子構象%蛋白質結閤%藥物耐受性
극뢰백균,폐염%DNA탁복이구매류,Ⅱ형%규낙동류%변이(유전학)%분자구상%단백질결합%약물내수성
Klebsiella pneumoniae%DNA topoisomerases,type Ⅱ%Quinolones%Variation (genetics)%Molecular conformation%Protein binding%Drug tolerance
目的 了解2种肺炎克雷伯菌DNA旋转酶A亚单位喹诺酮耐药决定区变异型与各种底物的结合能力.方法 参照野生型作同源建模获得2种肺炎克雷伯菌DNA旋转酶A亚单位变异型(Ⅰ型和FH型)立体结构,ArgusLab 4.1软件中的DOCK模块做DNA旋转酶A亚单位野生型和2种变异型与7种喹诺酮类药物分子对接,计算酶与底物结合自由能值(△G),并计算DNA旋转酶A亚单位氨基酸残基与环丙沙星相互作用原子对数量及距离.结果 肺炎克雷伯菌DNA旋转酶A亚单位变异型Ⅰ型、FH型与吡哌酸、环丙沙星、加替沙星结合自由能值分别为-26.607 50、-29.530 39、-29.493 09 kJ/mol,-26.696 44、-28.972 83、-29.590 50 kJ/mol;野生型分别为-27.188 82、-30.872 00、-30.244 04 kJ/mol,即吡哌酸、环丙沙星、加替沙星与2种变异型结合力下降,呈现耐药.Ⅰ型、FH型与左氧氟沙星结合自由能值为-29.013 81、-29.497 57 kJ/mol,野生型为-28.016 20 kJ/mol.Ⅰ型、FH型与萘啶酸、诺氟沙星、氧氟沙星结合自由能值有升有降.DNA旋转酶A亚单位野生型、Ⅰ型、FH型与环丙沙星相互作用形成原子对距离在5×10-10 m以内的分别有16对、2对和4对；形成原子对距离在4×10-10 m以内的只有8对,均为野生型.结论 肺炎克雷伯菌DNA旋转酶A亚单位2种变异型与环丙沙星结合力下降是耐药的形成因素.
目的 瞭解2種肺炎剋雷伯菌DNA鏇轉酶A亞單位喹諾酮耐藥決定區變異型與各種底物的結閤能力.方法 參照野生型作同源建模穫得2種肺炎剋雷伯菌DNA鏇轉酶A亞單位變異型(Ⅰ型和FH型)立體結構,ArgusLab 4.1軟件中的DOCK模塊做DNA鏇轉酶A亞單位野生型和2種變異型與7種喹諾酮類藥物分子對接,計算酶與底物結閤自由能值(△G),併計算DNA鏇轉酶A亞單位氨基痠殘基與環丙沙星相互作用原子對數量及距離.結果 肺炎剋雷伯菌DNA鏇轉酶A亞單位變異型Ⅰ型、FH型與吡哌痠、環丙沙星、加替沙星結閤自由能值分彆為-26.607 50、-29.530 39、-29.493 09 kJ/mol,-26.696 44、-28.972 83、-29.590 50 kJ/mol;野生型分彆為-27.188 82、-30.872 00、-30.244 04 kJ/mol,即吡哌痠、環丙沙星、加替沙星與2種變異型結閤力下降,呈現耐藥.Ⅰ型、FH型與左氧氟沙星結閤自由能值為-29.013 81、-29.497 57 kJ/mol,野生型為-28.016 20 kJ/mol.Ⅰ型、FH型與萘啶痠、諾氟沙星、氧氟沙星結閤自由能值有升有降.DNA鏇轉酶A亞單位野生型、Ⅰ型、FH型與環丙沙星相互作用形成原子對距離在5×10-10 m以內的分彆有16對、2對和4對；形成原子對距離在4×10-10 m以內的隻有8對,均為野生型.結論 肺炎剋雷伯菌DNA鏇轉酶A亞單位2種變異型與環丙沙星結閤力下降是耐藥的形成因素.
목적 료해2충폐염극뢰백균DNA선전매A아단위규낙동내약결정구변이형여각충저물적결합능력.방법 삼조야생형작동원건모획득2충폐염극뢰백균DNA선전매A아단위변이형(Ⅰ형화FH형)입체결구,ArgusLab 4.1연건중적DOCK모괴주DNA선전매A아단위야생형화2충변이형여7충규낙동류약물분자대접,계산매여저물결합자유능치(△G),병계산DNA선전매A아단위안기산잔기여배병사성상호작용원자대수량급거리.결과 폐염극뢰백균DNA선전매A아단위변이형Ⅰ형、FH형여필고산、배병사성、가체사성결합자유능치분별위-26.607 50、-29.530 39、-29.493 09 kJ/mol,-26.696 44、-28.972 83、-29.590 50 kJ/mol;야생형분별위-27.188 82、-30.872 00、-30.244 04 kJ/mol,즉필고산、배병사성、가체사성여2충변이형결합력하강,정현내약.Ⅰ형、FH형여좌양불사성결합자유능치위-29.013 81、-29.497 57 kJ/mol,야생형위-28.016 20 kJ/mol.Ⅰ형、FH형여내정산、낙불사성、양불사성결합자유능치유승유강.DNA선전매A아단위야생형、Ⅰ형、FH형여배병사성상호작용형성원자대거리재5×10-10 m이내적분별유16대、2대화4대；형성원자대거리재4×10-10 m이내적지유8대,균위야생형.결론 폐염극뢰백균DNA선전매A아단위2충변이형여배병사성결합력하강시내약적형성인소.
Objective To investigate the binding capacities of two variants of quinolone resistance-determining region in the DNA gyrase subunit A to substrates in Klebsiella pneumonia (K.pneumonia).Methods Tertiary structures of two variants (type Ⅰ and type FH) of quinolone resistance-determining region in the DNA gyrase subunit A in K.pneumonia were predicted by homology modeling referring to that of wild type.Then,DOCK module in ArgusLab 4.1 software was used to perform molecular docking of two variants and wild type to seven kinds of quinolones substrates,and calculate binding free energies (△G).Moreover,numbers and distances of interaction between amino acid residues of DNA gyrase subunit A and ciprofloxacin were calculated.Results Molecular docking showed that binding free energies of type Ⅰ and type FH to pipemidic acid,ciprofloxacin,gatifloxacin were-26.607 50,-29.530 39,-29.493 09 kJ/mol and-26.696 44,-28.972 83,-29.590 50 kJ/mol,respectively,which declined greater than those of wild type (-27.188 82,-30.872 00 and-30.244 04 kJ/mol,respectively) and showed drug resistance.While binding free energies of type Ⅰ and type FH to levofloxacin were-29.013 81 and-29.497 57kJ/mol,respectively,and that of wild type was-28.016 20 kJ/mol.The binding free energies of type Ⅰ and type FH to nalidixic acid,norfloxacin,ofloxacin increased or declined.Moreover,if distance was less than 5 angstroms,atom pairs formed between wild type of DNA gyrase subunit A and ciprofloxacin had 16 pairs,while type Ⅰ and type FH had 2 pairs and 4 pairs,respectively.If distance was less than 4 angstroms,atom pairs formed between wild type and ciprofloxacin had 8 pairs,while type Ⅰ and type FH had no atom pairs.Conclusion Decline of binding capacities of two variants of DNA gyrase subunit A in K.pneumonia to ciprofloxacin played a role in drug resistance.
