Structural basis of substrate specificity of Helix pomatia AMP deaminase and a chimeric ADGF adenosine deaminase

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

HPAMPD, an enzyme enriched in the foot muscle of mollusk Helix pomatia , exhibits deaminase activity on adenosine-5'-monophosphate (AMP). HPAMPD is first member a denosine d eaminase-related growth factor (ADGF) family to prefer nucleotide, AMP, over nucleoside, adenosine. To investigate substrate selectivity we determined its structure apo form and complex with adenosine analogs pentostatin (2'- deoxycoformycin) pentostatin-5'-monophosphate. Structurally, adopts fold similar human ADA2, ADGF member. has acquired ability interact 5'-monophosphate group AMP through polar charged residues located three key structural elements: (1) loop immediately following strand β1, (2) between helices αH αI, (3) end β5 adjacent loop. We engineered chimeric by integrating these elements from into another related nucleoside deaminase, A. californica ADGF. The efficiently deaminates demonstrating gained specificity, while retaining deamination Aplysia phosphate-binding feature hallmark nucleotide deaminases, conserved among N6-methyl-AMP (6mAMP) deaminases. discuss deaminases each distinct specificities for (AMP), methylated form, 6mAMP.

Language: Английский

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Advancing RNA phage biology through meta-omics

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(8)

Published: April 22, 2025

Abstract Bacteriophages with RNA genomes are among the simplest biological entities on Earth. Since their discovery in 1960s, they have been used as important models to understand principal processes of life, including translation and genetic code. While phages were generally thought rare oddities nature, meta-omics methods rapidly changing this simplistic view by studying diverse biomes unprecedented resolution. Metatranscriptomics dramatically expanded number known from tens thousands, revealed widespread abundance, discovered several new families potential largely unknown hosts, biology, environmental impact. At same time, (meta)genomic analyses bacterial hosts discovering an arsenal defense systems bacteria employ protect themselves predation, whose functions immunity against we only beginning understand. Here, I review how approaches advancing field phage biology a focus might fight them.

Language: Английский

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The Kongming defense: Host-pathogen battles take a new face

Engineering Microbiology, Journal Year: 2025, Volume and Issue: unknown, P. 100209 - 100209

Published: May 1, 2025

Language: Английский

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