Molecular structure and intermolecular interactions of N1'-methoxycarbonylbiotin methyl ester: a model for carboxybiotin.

Abstract

The crystal structure of N1'-methoxycarbonylbiotin methyl ester, a model for M'-carboxybiotin, has been determined. The In the first half-reaction, enzyme-bound biotin is carboxylated at Ni', generating N1'-carboxybiotin (II). In the second halfreaction, C02 is transferred, as a carboxyl group, from carboxybiotin to another molecule. Biotin enzymes are, in general, high molecular weight, multisubunit structures; the half-reactions generally occur at separate active sites which are located on different subunits of the enzymes.Here, we report the molecular structure of N1'-methoxycarbonylbiotin methyl ester (III), which is a model for Ni'-carboxybiotin (II). Structural results were obtained by using the technique of single-crystal x-ray diffraction. Previous crystallographic studies have established the molecular structures of free biotin (I) (2), dethiobiotin (3), azabiotin (4), oxybiotin, selenobiotin, biotin methyl ester, biotin sulfone, and biotin-d-sulfoxide, and carbobiotin (5). Differences between the molecular geometries and therefore the electronic configurations of the ureido moieties of I and III are of great interest because the ureido ring is the catalytically active portion of the biotin molecule. The previous studies have stressed the notion that, in free biotin and its'derivatives, the polarized forms of the biotin resomers (those with 'formal charge separation)

Comparison of the Structures and Vibrational Modes of Carboxybiotin and N-Carboxy-2-imidazolidone

“…A similar conformation was found in the ureido ring of the 6-31G* optimized structure and X-ray structure of chainless biotin . Table lists selected dihedral angles of the theoretical structure and compares them to those observed from X-ray structures of dethiobiotin, biotin, and methoxycarbonylbiotin methyl ester . It can be seen that the predicted dihedrals E and F for 2-methylbiotin are very close to the values for biotin.…”

“…6 Table 1 lists selected dihedral angles of the theoretical structure and compares them to those observed from X-ray structures of dethiobiotin, 18 biotin, 22 and methoxycarbonylbiotin methyl ester. 23 It can be seen that the predicted dihedrals E and F for 2-methylbiotin are very close to the values for biotin. The addition of the methyl group at C2 introduces a noticeable distortion to the mirror symmetry observed in chainless biotin, with the environments of the ureido, N1′, and N3′ hydrogen atoms in 4 being distinct.…”

Structural Analysis of Substrate, Reaction Intermediate, and Product Binding in Haemophilus influenzae Biotin Carboxylase

“…In contrast, the crystal structure of N1′-methoxycarbonyl biotin methyl ester not bound to protein shows the carboxymethyl ester moiety is coplanar with the ureido ring of biotin. 27 It is important to note that the methyl group of the carboxymethyl ester moiety does not interact with any active site amino acids and, therefore, is unlikely to influence the orthogonal orientation relative to the ureido ring of biotin.…”

Crystal Structure of the Carboxyltransferase Domain of the Oxaloacetate Decarboxylase Na+ Pump from Vibrio cholerae

“…Asp17 may function as the proton acceptor. 23 Please note that in the docking model the biotin has the correct orientation for nucleophilic attack by its carboxyl accepting nitrogen atom N1′. The free electron pair on N1′ is suitably oriented for nucleophilic addition of the carbamoyl carbon.…”