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Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract

The emergence of β-lactamase–producing Gram-negative bacteria represents a major global challenge due to increasing resistance to β-lactam antibiotics. In this study, we performed in silico structural and functional prediction of a newly identified β-lactamase protein sequence obtained from a Gram-negative bacterial isolate. Homology modeling was used to construct a reliable 3D model of the protein based on structurally resolved β-lactamases. The model was further evaluated using stereochemical validation parameters. Molecular docking was conducted to assess binding affinity and interaction patterns between the predicted β-lactamase and clinically relevant β-lactam antibiotics, including ampicillin, cefotaxime, and imipenem. The results revealed conserved catalytic residues typical of class A β-lactamases, strong binding affinities toward penicillin and cephalosporin substrates, and key hydrogen bond interactions within the active site. This study provides a structural framework for understanding the function of the new β-lactamase and offers insights for developing β-lactamase inhibitors targeting resistant Gram-negative pathogens.

Bahasa Abstract

Kemunculan bakteri Gram-negatif penghasil β-laktamase merupakan tantangan global utama karena meningkatnya resistensi terhadap antibiotik β-laktam. Dalam studi ini, kami melakukan prediksi struktural dan fungsional secara in silico terhadap sekuens protein β-laktamase yang baru diidentifikasi yang diperoleh dari isolat bakteri Gram-negatif. Pemodelan homologi digunakan untuk membangun model 3D protein yang andal berdasarkan β-laktamase yang strukturnya telah ditentukan. Model tersebut selanjutnya dievaluasi menggunakan parameter validasi stereokimia. Penambatan molekuler dilakukan untuk menilai afinitas pengikatan dan pola interaksi antara β-laktamase yang diprediksi dan antibiotik β-laktam yang relevan secara klinis, termasuk ampisilin, sefotaxim, dan imipenem. Hasilnya menunjukkan residu katalitik yang terkonservasi yang khas untuk β-laktamase kelas A, afinitas pengikatan yang kuat terhadap substrat penisilin dan sefalosporin, dan interaksi ikatan hidrogen utama di dalam situs aktif. Studi ini menyediakan kerangka struktural untuk memahami fungsi β-laktamase baru dan menawarkan wawasan untuk mengembangkan inhibitor β-laktamase yang menargetkan patogen Gram-negatif resisten.

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