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Nucleotide and AP sub 5 A complexes of porcine adenylate kinase: A sup 1 H and sup 19 F NMR study

Journal Article · · Biochemistry; (USA)
DOI:https://doi.org/10.1021/bi00436a029· OSTI ID:5352196
;  [1]
  1. Max Planck Institute for Medical Research, Heidelberg (West Germany)

Proton and fluorine nuclear magnetic resonance spectroscopies (NMR) were used as methods to investigate binary complexes between porcine adenylate kinase (AK{sub 1}) and its substrates. The authors also studied the interaction of fluorinated substrate analogues and the supposed bisubstrate analogue P{sup 1},P{sup 5}-bis(5{prime}-adenosyl) pentaphosphate (AP{sub 5}A) with AK{sub 1} in the presence of Mg{sup 2+}. The chemical shifts of the C8-H, C2-H, and ribose C1{prime}-H resonances of both adenosine units in stoichiometric complexes of AK{sub 1} with AP{sub 5}A in the presence of Mg{sup 2+} could be determined. The C2-H resonance of one of the adenine bases experiences a downfield shift of about 0.8 ppm on binding to the enzyme. {sup 19}F NMR chemical shifts of 9-(3-fluoro-3-deoxy-{beta}-D-xylofuranosyl)adenine triphosphate (3{prime}-F-X-ATP)-Mg{sup 2+} and 9-(3-fluoro-3-deoxy-{beta}-D-xylofuranosyl)adenine monophosphate (3{prime}-F-X-AMP) bound to porcine adenylate kinase could be determined. The different chemical shifts of the bound nucleotides suggest that their mode of binding is different. Free and bound 3{prime}-F-X-ATP are in fast exchange with respect to their {sup 19}F chemical shifts, whereas free and bound 3{prime}-F-X-ATP are in slow exchange on the NMR time scale in the absence as well as in the presence of Mg{sup 2+}. This information could be used to determine the apparent dissociation constants of the nucleotides and the 3{prime}-F-X analogues in the binary complexes. A strong nuclear Overhauser effect (NOE) could be detected between one of the two C2 protons of AP{sub 5}A and the C2 proton of the imidazole ring of His{sup 36}. This proton thus belongs to the site which was earlier suggested to be the ATP{center dot}Mg{sup 2+} site for the pig as well as for the rabbit enzyme.

OSTI ID:
5352196
Journal Information:
Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:10; ISSN 0006-2960; ISSN BICHA
Country of Publication:
United States
Language:
English