Acyl-coenzyme A-dependent N-acetyltransferases (AACs) catalyze the modification of aminoglycosides rendering the bacteria carrying such enzymes resistant to this class of antibiotics. Here we present the crystal structure of AAC(3)-Ia enzyme from Serratia marcescens in complex with coenzyme A determined to 1.8 Å resolution. This enzyme served as an architype for the AAC enzymes targeting the amino group at Position 3 of aminoglycoside main aminocyclitol ring. The structure of this enzyme has been previously determined only in truncated form and was interpreted as distinct from subsequently characterized AACs. The reason for the unusual arrangement of secondary structure elements of AAC(3)-Ia was not further investigated. By determining the full-length structure of AAC(3)-Ia we establish that this enzyme adopts the canonical AAC fold conserved across this family and it does not undergo through significant rearrangement of secondary structure elements upon ligand binding as was proposed previously. In addition, our results suggest that the C-terminal tail in AAC(3)-Ia monomer forms intramolecular hydrogen bonds that contributes to formation of stable dimer, representing the predominant oligomeric state for this enzyme.

中文翻译：

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结构的全长粘质沙雷氏菌乙酰转移酶AAC（3）-Ia与辅酶A复合。

酰基辅酶A依赖性N-乙酰基转移酶（AAC）催化氨基糖苷的修饰，使携带此类酶的细菌对此类抗生素具有抵抗力。在这里，我们介绍了来自Serratia marcescens的AAC（3）-Ia酶的晶体结构，辅酶A的复合物测定为1.8Å分辨率。该酶是针对氨基糖苷主氨基环糖醇环的3位氨基上的AAC酶的原型。该酶的结构先前仅以截短形式确定，并被解释为与随后表征的AAC不同。没有进一步研究AAC（3）-Ia二级结构元素排列异常的原因。通过确定AAC（3）-Ia的全长结构，我们确定该酶采用该家族中保守的经典AAC折叠，并且在配体结合后，它不会经历二级结构元件的显着重排，如先前所提出的。此外，我们的结果表明，AAC（3）-Ia单体中的C末端尾巴形成分子内氢键，有助于形成稳定的二聚体，代表该酶的主要低聚状态。