Structural and functional studies of SAV1707 from Staphylococcus aureus elucidate its distinct metal‐dependent activity and a crucial residue for catalysis

The metallo‐β‐lactamase fold is the most abundant metal‐binding domain found in two major kingdoms: bacteria and archaea. Despite the rapid growth in genomic information, most of these enzymes, which may play critical roles in cellular metabolism, remain uncharacterized in terms of structure and fun...

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Veröffentlicht in:Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2021-05, Vol.77 (5), p.587-598
Hauptverfasser: Kim, Dong-Gyun, Lee, Kyu-Yeon, Lee, Sang Jae, Cheon, Seung-Ho, Choi, Yuri, Lee, Hyung Ho, Ahn, Hee-Chul, Lee, Bong-Jin
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Sprache:eng
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Zusammenfassung:The metallo‐β‐lactamase fold is the most abundant metal‐binding domain found in two major kingdoms: bacteria and archaea. Despite the rapid growth in genomic information, most of these enzymes, which may play critical roles in cellular metabolism, remain uncharacterized in terms of structure and function. In this study, X‐ray crystal structures of SAV1707, a hypothetical metalloenzyme from Staphylococcus aureus, and its complex with cAMP are reported at high resolutions of 2.05 and 1.55 Å, respectively, with a detailed atomic description. Through a functional study, it was verified that SAV1707 has Ni2+‐dependent phosphodiesterase activity and Mn2+‐dependent endonuclease activity, revealing a different metal selectivity depending on the reaction. In addition, the crystal structure of cAMP‐bound SAV1707 shows a unique snapshot of cAMP that reveals the binding mode of the intermediate, and a key residue Phe511 that forms π–π interactions with cAMP was verified as contributing to substrate recognition by functional studies of its mutant. Overall, these findings characterized the relationship between the structure and function of SAV1707 and may provide further understanding of metalloenzymes possessing the metallo‐β‐lactamase fold. Crystal structures of apo and cAMP‐bound SAV1707, a member of the UPF0173 metal‐dependent hydrolase family from Staphylococcus aureus, were determined at 2.05 and 1.55 Å resolution, respectively, providing functional and structural insights into the catalytic mechanism of SAV1707.
ISSN:2059-7983
0907-4449
2059-7983
1399-0047
DOI:10.1107/S2059798321001923