Knox J R, Moews P C, Frere J M
Department of Molecular and Cell Biology, The University of Connecticut, Storrs, CT 06269-3125, USA.
Chem Biol. 1996 Nov;3(11):937-47. doi: 10.1016/s1074-5521(96)90182-9.
Two groups of penicillin-destroying enzymes, the class A and class C beta-lactamases, may have evolved from bacterial transpeptidases that transfer X-D-Ala-D-Ala peptides to the growing peptidoglycan during cell wall synthesis. Both the transpeptidases and the beta-lactamases are acylated by beta-lactam antibiotics such as penicillin, which mimic the peptide, but breakdown and removal of the antibiotic is much faster in the beta-lactamases, which lack the ability to process D-Ala-D-Ala peptides. Stereochemical factors driving this evolution in specificity are examined.
We have compared the crystal structures of two classes of beta-lactamases and a beta-lactam-sensitive D-alanyl-D-alanine carboxy-peptidase/transpeptidase (DD-peptidase). The class C beta-lactamase is more similar to the DD-peptidase than to another beta-lactamase of class A.
The two classes of beta-lactamases appear to have developed from an ancestral protein along separate evolutionary paths. Structural differentiation of the beta-lactamases from the DD-peptidases appears to follow differences in substrate shapes. The structure of the class A beta-lactamase has been further optimized to exclude D-alanyl peptides and process penicillin substrates with near catalytic perfection.
两类青霉素破坏酶，即A类和C类β-内酰胺酶，可能是从细菌转肽酶进化而来的。在细胞壁合成过程中，这些转肽酶会将X-D-丙氨酰-D-丙氨酸肽转移到正在生长的肽聚糖上。转肽酶和β-内酰胺酶都会被青霉素等β-内酰胺类抗生素酰化，这些抗生素可模拟肽段，但在缺乏处理D-丙氨酰-D-丙氨酸肽能力的β-内酰胺酶中，抗生素的分解和去除速度要快得多。本文研究了驱动这种特异性进化的立体化学因素。
我们比较了两类β-内酰胺酶以及一种对β-内酰胺敏感的D-丙氨酰-D-丙氨酸羧肽酶/转肽酶（DD-肽酶）的晶体结构。C类β-内酰胺酶与DD-肽酶的相似性高于与另一类A类β-内酰胺酶的相似性。
两类β-内酰胺酶似乎是沿着不同的进化路径从一种祖先蛋白发展而来的。β-内酰胺酶与DD-肽酶的结构差异似乎源于底物形状的不同。A类β-内酰胺酶的结构已进一步优化，以排除D-丙氨酰肽，并以近乎完美的催化效率处理青霉素底物。
