Puromycin‐hydrolizing peptidases have been described as members of the prolyl oligopeptidase peptidase family. These enzymes are present across all domains of life but still little is known of the homologs found in the pathogenic bacterium Mycobacterium tuberculosis. The crystal structure of a M. tuberculosis puromycin hydrolase peptidase has been determined at 3 Angstrom resolution, revealing a conserved prolyl oligopeptidase fold, defined by α/β‐hydrolase and β‐propeller domains with two distinctive loops that occlude access of large substrates to the active site. The enzyme displayed amino peptidase activity with a substrate specificity preference for hydrophobic residues in the decreasing order of phenylalanine, leucine, alanine and proline. The enzyme's active site is lined by residues Glu564 for the coordination of the substrates amino terminal moiety and His561, Val608, Tyr78, Trp306, Phe563 and Ty567 for the accommodation of hydrophobic substrates. The availability of a crystal structure for puromycin hydrolase of M. tuberculosis shall facilitate the development of inhibitors with therapeutic applications.

中文翻译：

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结核分枝杆菌嘌呤霉素水解酶显示脯氨酰寡肽酶折叠和酰基氨肽酶活性

嘌呤霉素水解肽酶已被描述为脯氨酰寡肽酶肽酶家族的成员。这些酶存在于生命的所有领域，但在致病细菌结核分枝杆菌中发现的同源物仍然知之甚少。结核分枝杆菌的晶体结构嘌呤霉素水解酶肽酶已在 3 埃分辨率下测定，揭示了保守的脯氨酰寡肽酶折叠，由 α/β-水解酶和 β-螺旋桨结构域定义，具有两个独特的环，可阻止大底物进入活性位点。该酶显示出氨肽酶活性，对疏水残基具有底物特异性，按苯丙氨酸、亮氨酸、丙氨酸和脯氨酸的递减顺序排列。该酶的活性位点由残基 Glu564 排列，用于协调底物氨基末端部分和 His561、Val608、Tyr78、Trp306、Phe563 和 Ty567，用于调节疏水性底物。结核分枝杆菌嘌呤霉素水解酶晶体结构的可用性将促进具有治疗应用的抑制剂的开发。