Miklós Cserzö

Different sequence environments of cysteines and half cystines in proteins Application to predict disulfide forming residues

Protein sequences are often derived by translating genetic information, rather than by classical protein sequencing. At the DNA level cysteines and half cystines are indistinguishable. Here we show that the sequential environments of ‘free’ cysteine and half cystine are different. A possible origin of this difference is discussed and a simple method to predict cysteines and half cystines from the amino acid sequence is also presented.

Prion protein: Evolution caught en route

The prion protein displays a unique structural ambiguity in that it can adopt multiple stable conformations under physiological conditions. In our view, this puzzling feature resulted from a sudden environmental change in evolution when the prion, previously an integral membrane protein, got expelled into the extracellular space. Analysis of known vertebrate prions unveils a primordial transmembrane protein encrypted in their sequence, underlying this relocalization hypothesis. Apparently, the time elapsed since this event was insufficient to create a “minimally frustrated” sequence in the new milieu, probably due to the functional constraints set by the importance of the very flexibility that was created in the relocalization. This scenario may explain why, in a structural sense, the prion protein is still en route toward becoming a foldable globular protein.

Versatility of the 1,1′-binaphthyl-2,2′-dicarboxylic acid host in solid-state inclusion: crystal and molecular structures of the dimethylformamide (1 : 2), dimethyl sulphoxide (1 : 1), and bromobenzene (1 : 1) clathrates

The clathrate structures of the host 1,1′-binaphthyl-2,2′-dicarboxylic acid (1) with dimethylformamide, (2), dimethyl sulphoxide, (3), and bromobenzene, (4) as guest molecules have been studied. X-Ray structure analyses show that the capacity for inclusion is primarily dependent on the proton donor–acceptor (co-ordinating) ability of the host. Nevertheless, the structures are very different. In (2)[crystal data: a= 14.916 (13), b= 9.882(10), c= 17.128(13)A, β= 90.45(7)°, space group P21/c, Z= 4, Rf= 0.066 for 2 550 observations] the guest molecules can act both as proton donor and acceptor in hydrogen bonding with the host, in (3)[a= 12.912(5), b= 17.979(15), c= 9.702(7)A, β= 110.79(7)°, P21/n, Z= 4, Rf= 0.080 for 1 932 reflexions] the guest molecule acts as proton acceptor only, and in (4)[a= 9.955(2), b= 10.426(3), c= 12.005(3)A, α= 77.34(2), β= 93.02(2), γ= 104.59(2)°, P, Z= 2, Rf= 0.074 for 1 555 observations] a ‘true’ clathrate structure is established, with bromobenzene being incorporated in a hydrogen-bonded host matrix of (1). The decrease in co-ordinating bond strength between host and guest is also manifested in the gradual increase of disorder observed for these guest species. Conclusions concerning the clathrate formation selectivity of (1) are derived from the structural observations.

Crystal and molecular structure of the H-bonded complex between 1-chloro-2-hydroxynaphthalene-3-carboxylic acid and dimethylformamide (1∶1)

Crystal structure determination of the title complex reveals that the dimethylformamide solvent is bound to the carboxylic function of the hydroxy acid, in the form of a 7-membered hydrogen-bonded loop involving both the expected O-H⋯O and an apparently weak C-H⋯O interaction between host and guest. There is a strong intramolecular hydrogen bond between the phenolic OH and the carbonyl oxygen. Close packing of the complex units is afforded by a herringbone type alignment of host molecules.