Thiolate exchange in [TmR]ZnSR′ complexes and relevance to the mechanisms of thiolate alkylation reactions involving zinc enzymes and proteins

Identification of Essential Catalytic Residues of the Cyclase NisC Involved in the Biosynthesis of Nisin

“…The zinc site in other enzymes that alkylate thiols (38) is thought to have a finely balanced coordination environment that on the one end facilitates a role as a Lewis acid to lower the pK a of the thiol substrates (39 -41) and at the same time activates the thiolate for nucleophilic attack. The strong rate acceleration of thiolate alkylation by increasing the number of sulfur donors to the catalytic zinc has been established in several model studies on small molecule metal complexes with varying sets of donor ligands (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Indeed, upon substrate coordination, the zinc in NisC is liganded by three thiolates in the model (Fig.…”

Biomimetic Applications of Metal Systems Supported by Scorpionates

“…The three sulfur donors of the [HB(tim R ) 3 ] ligand system may be used to emulate the three cysteine residues in ALAD. In particular, the zinc hydroxide complex [HB(tim Ph ) 3 ]ZnOH complex (Fig 12b) 3 ] ligand serves the role of the three cysteine residues that remain bound to zinc during the course of the alkylation reaction Melnick et al, 2006). The thiolate complexes [HB(tim R ) 3 ]ZnSCH 2 C(O)N(H)Ph (R = Ph, tBu), which incorporate an N-H hydrogen bonding functionality, provide a more refined structural analogue for the Ada protein (Morlok et al, 2005 (Gorrell et al, 1990;Looney et al, 1995) (Gorrell et al, 1990;Dowling & Parkin, 1996;Ghosh & Parkin, 1998 (Fig.…”

Manganese(II) tri-tert-butoxysilanethiolate complexes with imidazole-based coligands: A neutral complex with four independent ligands and MNOS2 core (M=Mn) related to the liver alcohol dehydrogenase catalytic center (M=Zn)

“…Hydrogen atom positions were calculated, added to the structure and refined with usual constraints. Exceptionally, H atoms from hydroxyl group in methanol molecules in 3 and O7-H7 group in 4 as well as H atoms attached to nitrogen atom from imidazole ring (2)(3)(4) were revealed from the difference electrondensity map. H atoms in the solvating methanol molecule in 4 have their U iso fixed at 0.08.…”

“…They are potential sources of sulfide materials [1], some are used as catalysts [2], but they also gained wide interest because of their relevance to the active centers of several, cysteine rich metaloproteins [3]. Metal thiolate complexes served well as models especially for biological species containing Fe, Cu and Zn [4].…”

“…During investigations of thiolate complexes with bulky and hydrolytically stable ligand derived from tri-tert-butoxysilanethiol (Bu t O) 3 SiSH [16] we prepared compounds with three different ligands -silanethiolate, 2-methylpyridine and ammonia -½MfSSiðOBu t Þ 3 g 2 ðNH 3 Þð2-MePyÞ (M = Zn, Co) [17,18] and detected the formation of complexes with water or alcohol as fourth ligand ½CofSSiðOBu t Þ 3 g 2 ðLÞð2-MePyÞ (L = H 2 O or MeOH) although these could not be isolated [18]. LADH retains 70% of its activity, when Zn is exchanged for Co II [4].…”