In the quest for increased control and tuneability of organic patterns at metal surfaces, more and more systems emerge that rely upon coordination of metal adatoms by organic ligands using endgroups such as carbonitriles, amines, and carboxylic acids.[1] Such systems promise great flexibility in the size and geometry of the surface pattern through choice of the ligand shape, the number and arrangement of ligating endgroups, and the nature of the metal centers. Planar (trigonal or square) arrangements of ligands around metal centers occur most commonly as a result of attractive interactions of the ligands with the substrate. In contrast, in the solution phase planar, and in particular trigonal planar, arrangements are quite rare and generally require ligands whose nature (for example bidentate, pincer shape) forces planarity.Given the relatively short history of the field of surface coordination chemistry, compared to its solution-phase counterpart, it is of great interest to know which information can be gleaned from the latter to predict that for the former.
COMMUNICATIONScontaining chiral amino acids starting from appropriate ester derivatives that could not be achieved by conventional chemical methods.Limitations for the universal application of enzymatic peptide synthesis result from the restrictive specificity of proteases and from the risk of proteolytic cleavage of the starting materials and the product. Utilization of substrate mimetics that were originally named "inverse substrates" in trypsin-catalyzed peptide syntheses[l3I and of proteolytically inactive z y m~g e n s [~] in conjunction with the results shown here offer an enzymatic strategy with emerging practical relevance.
Carbanionic
intermediates play a central role in the catalytic transformations
of amino acids performed by pyridoxal-5′-phosphate (PLP)-dependent
enzymes. Here, we make use of NMR crystallography—the synergistic
combination of solid-state nuclear magnetic resonance, X-ray crystallography,
and computational chemistry—to interrogate a carbanionic/quinonoid
intermediate analogue in the β-subunit active site of the PLP-requiring
enzyme tryptophan synthase. The solid-state NMR chemical shifts of
the PLP pyridine ring nitrogen and additional sites, coupled with
first-principles computational models, allow a detailed model of protonation
states for ionizable groups on the cofactor, substrates, and nearby
catalytic residues to be established. Most significantly, we find
that a deprotonated pyridine nitrogen on PLP precludes formation of
a true quinonoid species and that there is an equilibrium between
the phenolic and protonated Schiff base tautomeric forms of this intermediate.
Natural bond orbital analysis indicates that the latter builds up
negative charge at the substrate Cα and positive
charge at C4′ of the cofactor, consistent with its role as
the catalytic tautomer. These findings support the hypothesis that
the specificity for β-elimination/replacement versus transamination
is dictated in part by the protonation states of ionizable groups
on PLP and the reacting substrates and underscore the essential role
that NMR crystallography can play in characterizing both chemical
structure and dynamics within functioning enzyme active sites.
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