H-bonding interactions and control of thiolate nucleophilicity and specificity in model complexes of zinc metalloproteins.
It is shown in model complexes designed to mimic the binding site of zinc-thiolate proteins that a single hydrogen bond between an amide N-H and a Zn-coordinated thiolate reduces its reactivity toward electrophiles by up to 2 orders of magnitude. In addition, we show that a single N-H...S hydrogen bond is sufficient to achieve near 100% regiospecificity of reaction between a strong, and hence inherently indiscriminate, alkylating agent like trimethyloxonium tetraflouroborate and a single sulfur in a dithiolate construct. The importance of these results in understanding how systems such as the zinc fingers of the GATA family and the E. coli DNA repair protein Ada, which share the same pseudotetrahedral structure and tetracysteinyl ligation around the zinc, can fulfill such widely divergent (structural vs reactive) roles and how specificity of reaction in such multi-thiolate containing systems can be achieved is discussed.
Smith
Jennifer N
JN
Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas 78666, USA.
Hoffman
Justin T
JT
Shirin
Zahida
Z
Carrano
Carl J
CJ
D001665:Binding Sites; D018360:Crystallography, X-Ray; D004260:DNA Repair; D029968:Escherichia coli Proteins / Q000737:chemistry; D006860:Hydrogen Bonding; D007700:Kinetics; D008667:Metalloproteins / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*; D016335:Zinc Fingers
D029968:Escherichia coli Proteins; D008667:Metalloproteins; D009942:Organometallic Compounds; D013438:Sulfhydryl Compounds; D015032:Zinc