Bacteria express β-lactamase to counteract the bactericidal effects of β-lactam antibiotics, which are the most widely employed antibacterial drugs. In gram-negative bacteria, the expression of β-lactamase is generally regulated in response to the muropeptide that is generated from the peptidoglycan of the cell wall during β-lactam antibiotic challenge. The direct regulation of β-lactamase expression by β-lactams was recently reported in Vibrio parahaemolyticus, and this regulation is mediated by a two-component regulatory system that consists of the histidine kinase VbrK and the response regulator VbrR. VbrK directly recognizes β-lactam antibiotics using the periplasmic sensor domain (VbrK^SD), a PF11884 Pfam family member, and it delivers the β-lactam signal to VbrR to induce the transcription of the β-lactamase gene. To determine the structural features of VbrK^SD as the prototype of the PF11884 family and provide insights into the β-lactam antibiotic-binding mode of VbrK^SD, we determined the crystal structure of VbrK^SD at 1.65 Å resolution. VbrK^SD folds into a unique curved rod-like structure that has not been previously reported in other families. VbrK^SD consists of two domains (D1 and D2). The D1 domain contains two helix-decorated β-sheets, and the D2 domain adopts a helix-rich structure. VbrK^SD features two terminal disulfide bonds, which would be the canonical property of the PF11884 family. In the VbrK^SD structure, the L82 residue, which was previously shown to play a key role in β-lactam antibiotic recognition, forms a pocket along with its neighboring hydrophobic or positively charged residues.

细菌表达β-内酰胺酶以抵消β-内酰胺抗生素的杀菌作用，后者是应用最广泛的抗菌药物。在革兰氏阴性细菌中，β-内酰胺酶的表达通常响应于在β-内酰胺抗生素攻击期间从细胞壁的肽聚糖产生的多肽而受到调节。最近在副溶血性弧菌中报道了β-内酰胺对β-内酰胺酶表达的直接调节，并且该调节由包括组氨酸激酶VbrK和应答调节剂VbrR的两组分调节系统介导。VbrK使用周质传感器域直接识别β-内酰胺抗生素（VbrK ^SD），它是PF11884 Pfam家族成员，它将β-内酰胺信号传递给VbrR，以诱导β-内酰胺酶基因的转录。为了确定作为PF11884家族原型的VbrK ^SD的结构特征，并提供对VbrK ^SD的β-内酰胺抗生素结合模式的见解，我们确定了1.65Å分辨率的VbrK ^SD的晶体结构。VbrK ^SD可以折叠成独特的弯曲杆状结构，以前在其他家族中没有报道过。VbrK ^SD包含两个域（D1和D2）。D1域包含两个螺旋装饰的β-折叠，D2域采用富含螺旋的结构。VbrK ^SD具有两个末端二硫键，这是PF11884系列的规范特性。在VbrK ^SD结构中，先前显示在L-内酰胺抗生素识别中起关键作用的L82残基与其相邻的疏水或带正电荷的残基一起形成一个囊袋。