Crystal structures of <scp>APRT</scp> from <i>Francisella tularensis</i> – an N–H···N hydrogen bond imparts adenine specificity in adenine phosporibosyltransferases

Pavithra, G.C.; Ramagopal, U.A.

doi:10.1111/febs.14481

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References 47 publications

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“…The reaction catalyzed by APRT has been proposed to involve an oxacarbenium transition state in which the adenine leaving group is activated by N7 protonation (Figure S31). In the canonical APRTs, the proton is donated by a conserved glutamate residue (Glu104 in human APRT) located in the flexible catalytic loop (Figure A). − An exception to this rule is the Sulfolobus solfataricus APRT in which this catalytic function results from the β-carboxylate of an aspartate residue positioned in the PRPP binding motif . In GvmE, the homologous position in the flexible catalytic loop is occupied by a glycine (Figure S32).…”

Section: Resultsmentioning

confidence: 99%

Guvermectin Biosynthesis Revealing the Key Role of a Phosphoribohydrolase and Structural Insight into the Active Glutamate of a Noncanonical Adenine Phosphoribosyltransferase

et al. 2023

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Guvermectin is a novel plant growth regulator that has been registered as a new agrochemical in China. It is an adenosine analogue with an unusual psicofuranose instead of ribose. Herein, the gene cluster responsible for guvermectin biosynthesis in Streptomyces caniferus NEAU6 is identified using gene interruption and heterologous expression experiments. A key intermediate psicofuranine 6′-phosphate (PMP) is chemically synthesized, and the functions of GvmB, C, D, and E are verified by individual stepwise enzyme reactions in vitro. The results also show that the biosynthesis of guvermectin is coupled with adenosine production by a single cluster. The higher catalytic efficiency of GvmB on PMP than AMP ensures the effective biosynthesis of guvermectin. Moreover, a phosphoribohydrolase GvmA is employed in the pathway that can hydrolyze AMP but not PMP and shows higher catalytic efficiency for the AMP hydrolysis than that of the AMP dephosphorylation by GvmB, leading to shunting of adenosine biosynthesis toward the production of guvermectin. Finally, the crystal structure of GvmE in complex with the product PMP has been solved. Glu160 at the C-terminal is identified as the acid/base for protonation/deprotonation of N7 of the adenine ring, demonstrating that GvmE is a noncanonical adenine phosphoribosyltransferase.

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Section: Resultsmentioning

confidence: 99%

Guvermectin Biosynthesis Revealing the Key Role of a Phosphoribohydrolase and Structural Insight into the Active Glutamate of a Noncanonical Adenine Phosphoribosyltransferase

et al. 2023

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Crystal structures of APRT from Francisella tularensis – an N–H···N hydrogen bond imparts adenine specificity in adenine phosporibosyltransferases

Abstract: EC 2.4.2.7 DATABASE: Structural data are available in Protein Data Bank (PDB) under the accession numbers 5YW2 and 5YW5.

Cited by 1 publication

References 47 publications

Guvermectin Biosynthesis Revealing the Key Role of a Phosphoribohydrolase and Structural Insight into the Active Glutamate of a Noncanonical Adenine Phosphoribosyltransferase

Guvermectin Biosynthesis Revealing the Key Role of a Phosphoribohydrolase and Structural Insight into the Active Glutamate of a Noncanonical Adenine Phosphoribosyltransferase

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