Crystal structure of the Escherichia coli peptide deformylase
Crystal structure of the Escherichia coli peptide deformylase
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DOI：
10.1021/bi9711543
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发表时间：
1997-11-11
期刊：
影响因子：
2.9
通讯作者：
Pei, DH
中科院分区：
文献类型：
--
作者：
Chan, MK;Gong, WM;Pei, DH
细菌中蛋白质的合成涉及N-末端甲硫氨酸的脱乙酰和脱乙酰。由于真核生物的蛋白质生物合成机制不同，肽脱甲酰基酶，细菌的酶负责去甲酰基，代表了抗生素研究的潜在目标。本文报道了含锌大肠杆菌肽脱甲酰基酶的结晶和2.9埃X射线结构解。而一级序列、三级结构和配位半胱氨酸的使用表明E.脱甲酰基酶属于金属蛋白酶的一个新的亚家族，金属周围的环境似乎与嗜热菌蛋白酶家族的活性位点具有很强的几何相似性，这表明它们的水解机制可能相似。另一个重要的问题是酶对N-甲酰化底物的特异性超过N-乙酰化底物的起源。基于结构，特异性似乎是由氢键相互作用和空间因素导致的，氢键相互作用使底物定向裂解，空间因素物理限制了N-末端羰基的大小。
Protein synthesis in bacteria involves the formylation and deformylation of the N-terminal methionine. As eukaryotic organisms differ in their protein biosynthetic mechanisms, peptide deformylase, the bacterial enzyme responsible for deformylation, represents a potential target for antibiotic studies. Here we report the crystallization and 2.9 Angstrom X-ray structure solution of the zinc containing Escherichia coli peptide deformylase. While the primary sequence, tertiary structure, and use of coordinated cysteine suggest that E. call deformylase belongs to a new subfamily of metalloproteases, the environment around the metal appears to have strong geometric similarity to the active sites of the thermolysin family, This suggests a possible similarity in their hydrolytic mechanisms. Another important issue is the origin of the enzyme's specificity for N-formylated over N-acetylated substrates. Based on the structure, the specificity appears to result from hydrogen-bonding interactions which orient the substrate for cleavage, and steric factors which physically limit the size of the N-terminal carbonyl group.