An iron hydroxide moiety in the 1.35 A resolution structure of hydrogen peroxide derived myoglobin compound II at pH 5.2.

The biological conversions of O(2) and peroxides to water as well as certain incorporations of oxygen atoms into small organic molecules can be catalyzed by metal ions in different clusters or cofactors. The catalytic cycle of these reactions passes through similar metal-based complexes in which one oxygen- or peroxide-derived oxygen atom is coordinated to an oxidized form of the catalytic metal center. In haem-based peroxidases or oxygenases the ferryl (Fe(IV)O) form is important in compound I and compound II, which are two and one oxidation equivalents higher than the ferric (Fe(III)) form, respectively. In this study we report the 1.35 A structure of a compound II model protein, obtained by reacting hydrogen peroxide with ferric myoglobin at pH 5.2. The molecular geometry is virtually unchanged compared to the ferric form, indicating that these reactive intermediates do not undergo large structural changes. It is further suggested that at low pH the dominating compound II resonance form is a hydroxyl radical ferric iron rather than an oxo-ferryl form, based on the short hydrogen bonding to the distal histidine (2.70 A) and the Fe...O distance. The 1.92 A Fe...O distance is in agreement with an EXAFS study of compound II in horseradish peroxidase.

L-Phenylalanyl-L-alanine dihydrate.

A new type of molecular arrangement for dipeptides is observed in the crystal structure of L-phenylalanyl-L-alanine dihydrate, C12H16N2O3-2H2O. Two L-Phe and two L-Ala side chains aggregate into large hydrophobic columns within a three-dimensional hydrogen-bond network.

Nanotube formation by hydrophobic dipeptides.

A wide range of applications has been suggested for peptide-based nanotubes, which first attracted considerable interest as model systems for membrane channels and pores. The intriguing and unprecedented observation of nanotube formation by supramolecular self-assembly of the four dipeptides L-Leu-L-Leu, L-Leu-L-Phe, L-Phe-L-Leu and L-Phe-L-Phe is described here. These simple compounds crystallize with hydrogen-bonded head-to-tail chains in the shape of helices with four to six peptide molecules per turn. The resulting structures have chiral hydrophilic channels with a van der Waals' diameter up to 10 A.

An NH3+...phenyl interaction in L-phenylalanyl-L-valine.

One of the amino H atoms of L-phenylalanyl-L-valine, C(14)H(20)N(2)O(3), participates in a rare secondary interaction in being accepted by the aromatic ring of the phenylalanine side chain. The phenyl group is also a donor in a weak hydrogen bond to the peptide carbonyl group.

Selective solvent inclusion as a tool for mapping molecular properties in crystal structures: a diethylstilbestrol example.

Useful information about hydrogen bonding, the preferred modes of hydrophobic interaction and conformational preferences of a specific molecule can be obtained from cocrystallization of the solute with a selected series of solvent molecules. This method is used in a study of nine different crystal structures of diethylstilbestrol (DES) solvates. It is shown that solvent inclusion results not only in stronger hydrogen bonds, but usually also in a larger number of favorable C-H.pi interactions between DES molecules. Furthermore, solvent molecules such as DMSO, DMF, acetonitrile and acetone demonstrate important hydrogen-bond donating properties in addition to their more familiar role as hydrogen-bond acceptors. Molecular conformations in the crystal structures compare favorably with results from molecular mechanics calculations.

Non-centrosymmetric racemates: space-group frequencies and conformational similarities between crystallographically independent molecules.

DL-Allylglycine (DL-2-amino-4-pentenoic acid, C5H9NO2) yields crystals with Pca2(1) symmetry and two crystallographically independent yet pseudo-inversion-related enantiomers. The distribution among the common space groups of other crystalline racemates with more than one molecule in the asymmetric unit has been established. The conformational similarities between crystallographically independent enantiomers in 114 non-centrosymmetric racemates were quantified using the r.m.s. deviation for a molecular superposition. The analysis shows that in the majority of crystals the conformations of the crystallographically independent molecules are very similar with mean r.m.s. deviation = 0.190 A. In almost 80% of the structures the mean r.m.s. deviations is in the interval 0-0.2 A. It is estimated that racemates constitute 23% of the centrosymmetric organic structures in the Cambridge Structural Database.

Structural relationships in crystals accommodating different stereoisomers of 2-amino-3-methylpentanoic acid.

A reinvestigation of the crystal structure of the 1:1 mixture of the two racemates DL-isoleucine and DL-allo-isoleucine, with a detailed analysis of interatomic distances between alternative side-chain positions, reveals a systematic distribution of the four stereoisomers in this crystal. Two different molecular chains exist in the crystal and each such chain accommodates a single diastereomeric pair only (L-isoleucine:D-allo-isoleucine or D-isoleucine:L-allo-isoleucine). The crystal is built up by a stacking of such chains in two dimensions and three different packing modes for the two types of chains are discussed. Crystallization experiments of the two individual racemates in the 1:1 mixture of DL-isoleucine:DL-allo-isoleucine have been undertaken. The structure of the racemate DL-isoleucine is presented. The molecular arrangements in this racemate and the 1:1 DL-isoleucine:DL-allo-isoleucine mixture are closely related. Furthermore, the spontaneous resolution of enantiomers upon crystallization of the other racemate, DL-allo-isoleucine, is rationalized on the basis of the aforementioned analysis of interatomic distances in the 1:1 DL-isoleucine:DL-allo-isoleucine complex. Structural data for a new L-isoleucine: D-allo-isoleucine complex are also given.

Glycyl-L-leucyl-L-tyrosine dihydrate 2-propanol solvate.

The asymmetric unit (C17H25N3O5.C3H8O.2H2O) consists of two crystallographically independent peptide molecules, A and B, with different conformations, chi 1(2) being trans and gauche- for the Leu residues in molecules A and B, respectively. The backbone conformation of both peptide molecules resembles that of the beta-pleated sheet arrangement found in proteins. Comparison with two other structures containing the tripeptide Gly-L-Leu-L-Tyr reveals almost identical molecular conformations, and in one instance also a common packing pattern.

NMR and molecular dynamics study of the tripeptide L-pyroglutamyl-L-histidylglycine.

The 1H spectrum of L-pyroglutamyl-L-histidylglycine in DMSO-d6 and 1H and 13C NMR spectra in D2O at pH 4.26 to 8.90 have been analysed. 3JHH vicinal coupling constants were used to determine rotamer populations by means of the Karplus equation. Viable molecular geometries were obtained with the aid of molecular dynamics simulations including water as solvent. In DMSO and in aqueous solution at low pH two stable conformations were identified which both have an intramolecular hydrogen bond between the histidine side chain and the C-terminal carboxylate group.

Structure of a 1:1 complex between L-Asp-L-Phe and L-His-Gly.

Both molecules occur in slightly folded conformations, characterized by phi 2 = -93.7 degrees in L-His-Gly and an unusual phi 2 = 60.2 degrees in L-Asp-L-Phe. The peptide linkage of L-His-Gly displays a substantial deviation from planarity with omega 1 = -163.5 degrees. The crystal packing is arranged in thick hydrophilic layers separated by hydrophobic sheets composed of L-Phe aromatic side chains. There are numerous hydrogen bonds, including an extremely short contact [O...N = 2.532 (6) A] between the ionized L-Asp and L-His side chains.

Structure of L-phenylalanine L-phenylalaninium formate.

C9H11NO2.C9H12NO2+.CHO2-, M(r) = 376.41, monoclinic, P2(1), a = 11.507 (6), b = 5.638 (3), c = 14.610 (5) A, beta = 100.65 (4) degrees, V = 932 (1) A3, Z = 2, Dx = 1.342 g cm-3, lambda(Mo K alpha) = 0.7107 A, mu = 0.94 cm-1, F(000) = 400, T = 295 K, final R = 0.047 for 2693 observed reflections. The phenylalanine zwitterion and the phenylalanine cation form a Speakman-salt-type hydrogen bond [O ... O = 2.496 (3) A]. Aromatic side chains constitute a thick hydrophobic layer with edge-to-face interactions between the phenyl rings.

Hydrogen bond connectivity patterns and hydrophobic interactions in crystal structures of small, acyclic peptides.

Crystal structures of all available unblocked linear peptides with two to five residues were retrieved from the Cambridge Structural Database and their intermolecular contacts and packing modes studied using molecular graphics. This survey reveals that interactions between hydrophobic portions of the molecules are critically important in determining the overall features of their crystal packing patterns. Distinct hydrophobic columns or layers are observed in almost all crystal structures. Analyses of the relationships between these interactions and crystal growth properties of small peptides are given. It is suggested that needle growth is promoted by hydrophobic packing, usually along a short crystallographic axis (4.6-6.0 angstroms). Also contributing to these morphologic characteristics are entropic factors associated with hydrophobic aggregation as well as tightly bound water molecules on hydrophobic faces. The paper also provides a comprehensive overview of hydrogen bond patterns in acyclic peptide crystals. It is demonstrated that one of their primary roles is to provide a scaffolding within which hydrophobic groups can aggregate. Even though there is a high density of hydrogen bonds in the crystals, often with complex patterns and networks, certain motifs are found to recur in a number of structures indicating specific hydrogen bond preferences. Water, for example, is an integral part of the hydrogen bond networks in these crystals, usually acting as the primary donor for main-chain carboxylate groups in peptide hydrates.

Crystal and molecular structures of the isomeric dipeptides alpha-L-aspartyl-L-alanine and beta-L-aspartyl-L-alanine.

The crystal and molecular structures of the alpha- and beta-L-Asp isomers of L-aspartyl-L-alanine have been determined at 120 K using 1226 and 1609 reflections (I greater than 2.5 sigma I), respectively. The space group for the alpha-isomer is P2(1), with cell parameters a = 4.788(1), b = 16.943(4), c = 5.807(1) A and beta = 107.55(2) degrees; final R factor 0.042. The space group for the beta-isomer is P2(1)2(1)2(1) with a = 4.845(1), b = 9.409(2) and c = 19.170(3) A; final R-factor 0.047. The two peptides crystallize as zwitterions with the side-chain acidic groups ionized. Each molecule adopts a trans configuration at the peptide bond with both carboxyl groups situated on the same side of the peptide plane. The geometries of the aspartyl moieties do, however, differ in the two structures. The peptide bond is significantly longer in the beta-isomer than in the alpha-isomer, with C-N 1.344(3) and 1.328(4) A, respectively. A very short intermolecular carboxyl...carboxyl hydrogen bond (O...O = 2.502(4) A) is observed in the crystals of the alpha-isomer.

Crystal and molecular structure of aspartame X HCl X 2H2O.

The crystal and molecular structure of the hydrochloride salt of the peptide sweetener aspartame (alpha-L-Asp-L-Phe methyl ester) has been determined at 120 K using 3877 reflections with I greater than 2.5 sigma I. Space group P2(1)2(1)2(1), cell dimensions a = 6.768(1), b = 9.796(1) and c = 26.520(3) A; final R factor 0.033. While the N-terminal L-Asp group in the structure of aspartame itself forms a six-membered ring with an intramolecular hydrogen bond between the carboxylate and the protonated amino terminus, the corresponding group in the hydrochloride adopts a completely different conformation with a weak intramolecular hydrogen bond between the carboxyl group and the N atom of the L-Phe residue. The L-Phe methyl ester moiety is rather similar in the two structures. Of the many possible conformations of aspartame, only one may be expected to function as a substrate at the receptor site for sweet taste, and a proposal is made for this active conformation.