VANCOMYCIN RESISTANCE - STRUCTURE OF D-ALANINE-D-ALANINE LIGASE AT 2.3-ANGSTROM RESOLUTION
VANCOMYCIN RESISTANCE - STRUCTURE OF D-ALANINE-D-ALANINE LIGASE AT 2.3-ANGSTROM RESOLUTION
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DOI：
10.1126/science.7939684
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发表时间：
1994-10-21
期刊：
影响因子：
56.9
通讯作者：
KNOX, JR
中科院分区：
文献类型：
--
作者：
FAN, C;MOEWS, PC;KNOX, JR
用X射线衍射法测定了大肠杆菌ddlB基因的D-丙氨酸：D-丙氨酸连接酶与S、R-甲基亚膦和三磷酸腺苷共结晶的分子结构，分辨率为2.3埃。提出了一种催化两种D-丙氨酸底物连接的机理，其中一个螺旋偶极和一个由酪氨酸、丝氨酸和谷氨酸组成的氢键三元组协助结合和去质子化步骤。通过序列比较发现，在对万古霉素耐药的肠球菌中发现的D-丙氨酸：D-乳酸连接酶(VANA)中存在一个不同的三联体。提出了VANA特异性改变的分子机制。
The molecular structure of the D-alanine:D-alanine ligase of the ddlB gene of Escherichia coli, co-crystallized with an S,R-methylphosphinate and adenosine triphosphate, was determined by x-ray diffraction to a resolution of 2.3 angstroms. A catalytic mechanism for the ligation of two D-alanine substrates is proposed in which a helix dipole and a hydrogen-bonded triad of tyrosine, serine, and glutamic acid assist binding and deprotonation steps. From sequence comparison, it is proposed that a different triad exists in a recently discovered D-alanine:D-lactate ligase (VanA) present in vancomycin-resistant enterococci. A molecular mechanism for the altered specificity of VanA is suggested.