Stereochemical control over Mn(II)-Thio versus Mn(II)-Oxy coordination in adenosine 5 prime -O-(1-thiodiphosphate) complexes at the active site of creatine kinase

Journal Article · Tue Feb 21 04:00:00 EST 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00430a026· OSTI ID:5719193

Smithers, G W; Sammons, R D; Goodhart, P J; LoBrutto, R; Reed, G H ^[1]

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1. Univ. of Wisconsin, Madison (USA)

The stereochemical configurations of the Mn(II) complexes with the resolved epimers of adenosine 5{prime}-O-(1-thiodiphosphate) (ADP{alpha}S), bound at the active site of creatine kinase, have been determined in order to assess the relative strengths of enzymic stereoselectivity versus Lewis acid/base preferences in metal-ligand binding. Electron paramagnetic resonance (EPR) data have been obtained for Mn(II) in anion-stabilized, dead-end (transition-state analogue) complexes, in ternary enzyme-Mn{sup II}ADP{alpha}S complexes, and in the central complexes of the equilibrium mixture. The modes of coordination of Mn(II) at P{sub alpha} in the nitrate-stabilized, dead-end complexes with each epimer of ADP{alpha}S were ascertained by EPR measurements with (R{sub p})-({alpha}-{sup 17}O)ADP{alpha}S and (S{sub p})-({alpha}-{sup 17}O)ADP{alpha}S. A reduction in the magnitude of the {sup 55}Mn hyperfine coupling constant in the spectrum for the complex containing (S{sub p})-ADP{alpha}S is indicative of Mn(II)-thio coordination at P{sub alpha}. The results indicate that a strict discrimination for a unique configuration of the metal-nucleotide substrate is expressed upon binding of all of the substrates to form the active complex (or an analogue thereof). This enzymic stereoselectivity provides sufficient binding energy to overcome an intrinsic preference for the hard Lewis acid Mn(II) to coordinate to the hard Lewis base oxygen.

• OSTI ID: 5719193
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:4; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADP
COMPLEXES
ELECTRON SPIN RESONANCE
ENZYMES
EVEN-ODD NUCLEI
HYPERFINE STRUCTURE
INTERMEDIATE MASS NUCLEI
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MANGANESE 55
MANGANESE COMPLEXES
MANGANESE ISOTOPES
MUSCLES
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
OXYGEN 17
OXYGEN ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
RESONANCE
STABLE ISOTOPES
STEREOCHEMISTRY
SUBSTRATES
TRANSFERASES
TRANSITION ELEMENT COMPLEXES