The structure and properties of flavins: Molecular orbital study based on totally optimized geometries. I. Molecular geometry investigations

Abstract

A mMOkUkabitplCdCUhOM ' (MnroO/3) using energy minimized mokcuh geomehies w m performed 011 oxidimd and reduced luminavin and related methylared isopllouzina. including cationic and anionic unpatvw of opimitcd geomu&s for thtse mokcular systems and provides the basis f a intcrpntation of but also highly fkxibk .bau thc N(5)-N(10) axis; only I kd/mol is requid for a 10" bend. N(10) is tuted irollbxuiac is comprtcd to k 0.76 Lul/mol (AH) lcss stable than its isomcr, OlloxrZine. Calcula-R c d d flntin BeDmctry depends 011 methyl rubstitutioa putern: N( 10) substituted fomu arc b a t with typicrl fold angles d 15Y, w h m u the unsubstitutcd reduced form is planar. Both oxidized and reduced form ale aim fkxible.Proton clffinitier wuc ulcui.ted for protonuion and deprotonatlon of oxidized and raluccd forms. Protoruth of oxidized fams is favored at N( I ) by 10-12 kal/mol and products somwhat nonplanar isoalloxuinium ions. In addition, AH for the two-electron reduction of lumiflrvin is estimated to be -19.7 L#l/mol.In this p~p r investigations of geomcaiC aspects an presented along with introductory and background mrtcrirl. Orbital ~mrmrr and ekctron diotribution srudi an prrscntcd in paper 11. spccics. ckrcapanalt withexperimcntpl geomeay, phototlazroa spectra. and Nkllt drcrsupports the chanicrl md bioio&d plopnic* oxidized famr ale shown to be most stable in h e p I . M I c O n f 1~ gawnlly OUI of thc plme slightly; aim, C(9)-methyl substiattion introduas fhmphxity. The uasubstitioar ~a l s o p r f o r n w d o o d as well asquinonc-mcthkle tautomenc . forms.

Crystal Structure of LAAO from Calloselasma rhodostoma with an l-Phenylalanine Substrate: Insights into Structure and Mechanism

“…Furthermore, theoretical studies by Hall and coworkers have shown that the redox state of the cofactor does affect geometry. 34 The pattern of substrate interactions in LAAO is nearly identical to that observed in DAAO (pdb code 1C0L). As discussed earlier by Pawelek et al, 12 the active sites in these two amino acid oxidases possess a high degree of enantiomeric conservation, relevant to the stereospecificity requirements of the substrate; Arg287, Tyr240 and Ser336 in the mirror image structure of DAAO correspond to Arg90, Tyr372 and Gly464, respectively, in LAAO.…”

Phage antibodies against an unstable hapten: Oxygen sensitive reduced flavin

“…In principle, this could reflect pH-dependent changes in conformation and/or charge in either the hapten or the antibody. Upon increasing the pH, the hapten adopts a negative charge on the pyrimidine nucleus of the ravin resulting in a redistribution of electron density [18] whereas the geometry of the hapten is similar in both ionization states [19]. As indicated by the order parameters (Table 1), flexibility of Fired in the antigen binding site is more restricted at the lower pH.…”

“…2A, curves b,c). This was unexpected as the rotational correlation time of a scFv molecule can be calculated according to Visser et al [17] as [10][11][12][13][14][15][16][17][18][19][20] ns. It appears that this discrepancy may be due to association of scFv molecules by hydrophobic interactions in the presence of salt, as in experiments performed in the absence of NaC1 (%crv shifts to about 20 ns (data not shown).…”

Time-resolved fluorescence analysis of the mobile flavin cofactor in p-hydroxybenzoate hydroxylase

“…From the point of view of dynamics, however, this step is particularly interesting as it necessarily involves significant mobility of the flavin. In addition, other than a possible bending of the isoalloxazine ring in the two-electron reduced state, 50,51 no indications exist that for completing the reaction cycle, conformations are required that are not in between the 'in' and 'out' conformation (including intermediate ones) as can be sampled in titration studies with different substrate analogues.…”