Crystal structure of formycin 5′-phosphate

An explanation for its tight binding to AMP nucleosidase

Vincent L. Giranda, Helen M. Berman, Vern L. Schramm

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Formycin 5′-monophosphate (FMP) is a strong competitive inhibitor of AMP nucleosidase with Km/Kis from 1200 to 2600 depending on the source of the enzyme. The crystal structure of FMP has been determined in order to understand the basis for its high affinity for AMP nucleosidases and other biological properties. The key structural features of FMP are (1) the base is the N(7)-H tautomer, (2) the N(3) of the base forms an intramolecular hydrogen bond to the phosphate oxygen O(1), (3) the glycosyl torsion angle is syn with O(4′)-C(1′) relative to C(9)-C(4) being -6.43°, and (4) the furanose ring pucker is C(3′)-endo, with a pseudorotation angle of 20.3′. The major difference between the AMP and FMP structures is that the glycosyl torsion angles differ by 190′. The computed conformational energy necessary to distort AMP so that it has the same glycosyl torsion angle as FMP is 4.6 kcal/mol. This corresponds to a 2100-fold difference in binding energy, in good agreement with the observed interaction between AMP nucleosidase and FMP.

Original languageEnglish (US)
Pages (from-to)5813-5818
Number of pages6
JournalBiochemistry
Volume27
Issue number15
StatePublished - 1988
Externally publishedYes

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AMP nucleosidase
Crystal structure
Torsional stress
Adenosine Monophosphate
Binding energy
formycin 5'-phosphate
Hydrogen
Hydrogen bonds
Phosphates
Oxygen

ASJC Scopus subject areas

  • Biochemistry

Cite this

Crystal structure of formycin 5′-phosphate : An explanation for its tight binding to AMP nucleosidase. / Giranda, Vincent L.; Berman, Helen M.; Schramm, Vern L.

In: Biochemistry, Vol. 27, No. 15, 1988, p. 5813-5818.

Research output: Contribution to journalArticle

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