Aqueous channels within apolar peptide aggregates: solvated helix of the &#945;-aminoisobutyric acid (Aib)-containing peptide Boc-(Aib-Ala-Leu)<SUB>3</SUB>-Aib-OMe.2H<SUB>2</SUB>O.CH<SUB>3</SUB>OH in crystals

Although the peptide Boc-Aibl-Ala2-Leu3- Aib4-Ala5-Leu6-Aib7-Ala8-Leu9-Aib10-OMe [with a t-butoxycarbonyl (Boc) blocking group at the amino terminus, a methyl ester (OMe) at the carboxyl terminus, and four &#945;-aminoisobutyric (Aib) residues] has a 3-fold repeat of residues, the helix formed by the peptide backbone is irregular. The carboxyl-terminal half assumes an &#945;-helical form with torsion angles ) and &#968; of approximately -60&#176; and -45&#176;, respectively, whereas the amino-terminal half is distorted by an insertion of a water molecule between the amide nitrogen of Ala5 [N(5)] and the carbonyl oxygen of Ala2 [0(2)]. The water molecule W(1) acts as a bridge by forming hydrogen bonds N(5).W(1) (2.93 A) and W(1)---0(2) (2.86 A). The distortion of the helix exposes the carbonyl oxygens of Aib1 and Aib4 to the outside environment, with the consequence that the helix assumes an amphiphilic character despite having all apolar residues. Neighboring helices in the crystal run in antiparallel directions. On one side of a helix there are only hydrophobic contacts with efficient interdigitation of leucine side chains with those from the neighboring helix. On the other side of the helix there are hydrogen bonds between protruding carbonyl oxygens and four water molecules that separate two neighboring helices. Along the helix axis the helices bind head-to-tail with a direct hydrogen bond N(2)-0(9) (3.00 A). Crystals grown from methanol/water solution are in space group P21, with a = 15.778 &#177; 0.004 A, b = 11.228 &#177; 0.002 A, c = 18.415 &#177; 0.003 A, &#946; = 102.10 &#177; 0.02&#176; and two formula units per cell for C49H88N1003. 2H2O.CH3OH. The overall agreement factor R is 7.5% for 3394 reflections observed with intensities &gt; 3&#963;(F), and the resolution is 0.90 A

Conformation of a 16-residue zervamicin IIA analog peptide containing three different structural features: 3<SUB>10</SUB>-helix, &#945;-helix, and &#946;-bend ribbon

Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib- Pro-Ala-Aib-Pro-Aib-Pro-Phe-OMe (where Boc is t-butoxycarbonyl and Aib is a-aminoisobutyric acid), a synthetic apolar analog of the membrane-active fungal peptide antibiotic zervamycin IIA, crystallizes in space group P1 with Z = 1 and cell parameters a = 9.086 &#177; 0.002 A:, b = 10.410 &#177; 0.002 A, c = 28.188 &#177; 0.004 A, &#945; = 86.13 &#177; 0.01&#176;, &#946; = 87.90 &#177; 0.01&#176;, and &#947; = 89.27 &#177; 0.01&#176;; overall agreement factor R = 7.3% for 7180 data (Fo &gt; 3&#963;) and 0.91-A resolution. The peptide backbone makes a continuous spiral that begins as a 310-helix at the N-terminus, changes to an &#945;-helix for two turns, and ends in a spiral of three &#946;-bends in a ribbon. Each of the &#946;-bends contains a proline residue at one of the corners. The torsion angles &#966;i range from -51&#176; to -91&#176; (average value -64&#176;), and the torsion angles &#968;i range from -1&#176; to -46&#176; (average value -31&#176;). There are 10 intramolecular NH-..OC hydrogen bonds in the helix and two direct head-to-tail hydrogen bonds between successive molecules. Two H20 and two CH3OH solvent molecules fill additional space with appropriate hydrogen bonding in the head-to-tail region, and two additional H20 molecules form hydrogen bonds with carbonyl oxygens near the curve in the helix at Pro-10. Since there is only one peptide molecule per cell in space group P1, the molecules repeat only by translation, and consequently the helices pack parallel to each other

Apolar peptide models for conformational heterogeneity, hydration, and packing of polypeptide helices: crystal structure of hepta- and octapeptides containing α-aminoisobutyric acid

The crystal structures of two helical peptides Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe (VALU-7) and Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe (VALU-8) have been determined to a resolution of 1.0 and 0.9 &#197;, respectively. Both the seven and eight residue peptides crystallize with two conformers per asymmetric unit. The VALU-8 conformers are completely helical and differ only at the C-terminus by a sign reversal of the &#966; &#968; angles of the last residue. One of the VALUE-7 conformers occurs as a normal -helix, whereas in the other, the N(7) = O(3) &#945;-type hydrogen bond is ruptured by the entry of a water molecule (W) into the helix, which in turn makes hydrogen bonds N(7)W = 2.97 &#197; and O(3) = 2.77 &#197;. The other side of the water molecule is surrounded by a hydrophobic pocket. These two conformers give a static representation of a step in a possible helix unwinding or folding process. In the value-8 crystal the helices aggregate in a parallel mode, whereas the aggregation is antiparallel in the VALUE-7 crystal. The crystal parameters are VALUE-7 crystal. The crystal parameters are VALUE-7, P21, a = 10.203 (3) &#197;, b = 19.744 (6) &#197;, c = 22.561 (6) &#197;, &#945; = 96.76&#176;, Z = 4, C38, H69N7O10&#183;0.5 H2O, R = 6.65% for 3674 reflections observed gt; 3&#963;(F): and VALU-8, P21, a; = 10.596 (4) &#197;, b = 27.57 (6) &#197;, c = 17.745 (5) &#197;, &#946; = 95.76 (3)&#176;, Z = 4, C42H76N76O11&#183;0.25 CH3OH, R = 6.63% for 4701 reflections observed gt; 3&#963;(F)

Helix packing of leucine-rich peptides: A parallel leucine ladder in the structure of Boc-Aib-Leu-Aib-Aib-Leu-Leu-Leu-Aib-Leu-Aib-OMe

The packing of peptide helices in crystals of the leucine-rich decapeptide Boc-Aib-Leu-Aib-Aib-Leu-Leu-Leu-Aib-Leu-Aib-OMe provides an example of ladder-like leucylleucyl interactions between neighboring molecules. The peptide molecule forms a helix with five 5&#8594;1 hydrogen bonds and two 4&#8594;1 hydrogen bonds near the C terminus. Three head-to-tail NH c O = C hydrogen bonds between helices form continuous columns of helices in the crystal. The helicial columns associate in an antiparallel fashion, except for the association of Leu Leu side chains, which occurs along the diagonal of the cell where the peptide helices are parallel. The peptide, with formula C56H102N10O13, crystallizes in space group P212121 with Z = 4 and cell parameters a = 16.774(3) &#197;, b = 20.032(3) &#197; and c = 20.117(3) &#197;; overall agreement factor R = 10.7% for 2014 data with |Fobs| &lt;3&#963;(F); resolution 1.0 &#197;

Aggregation studies in crystals of apolar helical peptides: Boc-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe

In the crystal, the backbone of Boc-(Aib-Val-Ala-Leu)2-Aib-OMc adopts a helical form with four &#945;-type hydrogen bonds in the middle, flanked by 310-type hydrogen bonds at either end. The helical molecules stack in columns with head-to-tail hydrogen bonds, either directly between NH and CO, or bridged by solvent molecules. The packing of the helices is parallel, even in space group P21. Cell parameters are a = 9.837(2) &#197;. b = 15.565(3) &#197;. c = 20.087(5) &#197;, &#946;= 96.42(2)&#176;. dcalc= 1.091 g/cm3 for C46H83,N9O12&#183; 1.5H2O&#183;0.67CH3OH. There appears to be some hydration of the backbone in this apolar helix

The RCSB Protein Data Bank: a redesigned query system and relational database based on the mmCIF schema

The Protein Data Bank (PDB) is the central worldwide repository for three-dimensional (3D) structure data of biological macromolecules. The Research Collaboratory for Structural Bioinformatics (RCSB) has completely redesigned its resource for the distribution and query of 3D structure data. The re-engineered site is currently in public beta test at http://pdbbeta.rcsb.org. The new site expands the functionality of the existing site by providing structure data in greater detail and uniformity, improved query and enhanced analysis tools. A new key feature is the integration and searchability of data from over 20 other sources covering genomic, proteomic and disease relationships. The current capabilities of the re-engineered site, which will become the RCSB production site at http://www.pdb.org in late 2005, are described

Helix aggregation in peptide crystals: occurrence of either all parallel or antiparallel packing motifs for α-helices in polymorphs of Boc-Aib-Ala-Leu-Ala-Leu-Aib-Leu-Ala-Leu-Aib-OMe

Three crystalline polymorphs of the helical decapeptide, Boc-Aib-Ala-Leu-Ala-Leu-Aib-Leu-Ala-Leu-Aib-OMe, have been obtained. Antiparallel helix aggregation is observed in crystals grown from methanol (A), while completely parallel packing is observed in crystals from isopropanol (B) or an ethylene glycol-ethanol mixture (C). Crystals B and C are very similar in molecular conformation and packing. The packing motifs in crystals A and B consist of rows of parallel molecules, with an almost identical arrangement in both crystals. In crystal A, adjacent rows assemble with helix axes pointed in oppsite directions, whereas in crystal B all rows assemble with helix axes pointed in the same direction. Electrostatic interactions between helix dipoles do not appear to be a major determinant of packing modes. The structures also do not provide a ready rationalization of packing preferences in terms of side-chain interactions or solvation. The -helix of the peptide in crystal A has seven 5&#8594;1 hydrogen bonds; the helix in crystal B is a mixed 3<SUB>10</SUB>/&#945;-helix. The crystal parameters are as follows. Crystal A: C<SUB>51</SUB>H<SUB>92</SUB>N<SUB>10</SUB>O<SUB>13</SUB>.CH<SUB>3</SUB>OH, space group P2<SUB>1</SUB> with a = 10.498(1) &#197;, b = 18.189(3) &#197;, c = 16.475(3) &#197;, &#946; = 99.28(1)&#176;, Z = 2, R = 9.6% for 1860 data. Crystal B: C<SUB>51</SUB>H<SUB>92</SUB>N<SUB>10</SUB>O<SUB>13</SUB>.C<SUB>3</SUB>H<SUB>7</SUB>OH, space group P2<SUB>1</SUB> with a = 10.534(1) &#197;, b = 28.571(4) &#197;, c = 11.055(2) &#197;, &#946;= 95.74(1)&#176;, Z = 2, R = 6.5% for 3251 data. Crystal C: C<SUB>51</SUB>H<SUB>92</SUB>N<SUB>10</SUB>O<SUB>13</SUB>.C<SUB>2</SUB>H<SUB>5</SUB>OH, space group P2<SUB>1</SUB>, with a = 10.450(1) &#197;, b = 28.442(5) &#197;, c = 11.020(2) &#197;, &#946;= 95.44(1)&#176;, Z = 2, R = 14.8% (isotropic) for 1948 data

Modular design of synthetic protein mimics. characterization of the helical conformation of a 13-residue peptide in crystals

The incorporation of &#945;-aminoisobutyryl (Aib) residues into peptide sequences facilitates helical folding. Aib-containing sequences have been chosen for the design of rigid helical segments in a modular approach to the construction of a synthetic protein mimic. The helical conformation of the synthetic peptide Boc-Aib-(Val-Ala-Leu-Aib)<SUB>3</SUB>-OMe in crystals is established by X-ray diffraction. The 13-residue apolar peptide adopts a helical form in the crystal with seven &#945;-type hydrogen bonds in the middle and <SUP>3</SUP>(10)-type hydrogen bonds at either end. The helices stack in columns, zigzag rather than linear, by means of direct NH...OC head to tail hydrogen bonds. Leucyl side chains are extended on one side of the helix and valyl side chains on the other side. Water molecules form hydrogen bonds with several backbone carbonyl oxygens that also participate in &#945;-helix hydrogen bonds. There is no apparent distortion of the helix caused by hydration. The space group is P2<SUB>1</SUB>2<SUB>1</SUB>2<SUB>1</SUB>, with a = 9.964 (3) &#197;, b = 20.117 (3) &#197;, c = 39.311 (6) &#197;, Z = 4, and dx = 1.127 g/cm<SUP>3</SUP> for C<SUB>64</SUB>H<SUB>106</SUB>N<SUB>13</SUB>O<SUB>16</SUB>.1.33H<SUB>2</SUB>O. The final agreement factor R was 0.089 for 3667 data observed &gt; 3&#963;(F) with a resolution of 0.9 &#197;

Unfolding of an α-helix in peptide crystals by solvation: conformational fragility in a heptapeptide

The structure of the peptide Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe has been determined in crystals obtained from a dimethylsulfoxide-isopropanol mixture. Crystal parameters are as follows: C<SUB>38</SUB>H<SUB>69</SUB>N<SUB>7</SUB>O<SUB>10</SUB> · H<SUB>2</SUB>O · 2C<SUB>3</SUB>H<SUB>7</SUB>OH, space group P2<SUB>1</SUB>, a = 10.350 (2) Å, b = 26.084 (4) Å, c = 10.395(2) Å,β = 96.87(12), Z = 2, R = 8.7% for 2686 reflections observed > 3.0 σ (F). A single 5 →1 hydrogen bond is observed at the N-terminus, while two 4 →1 hydrogen bonds characteristic of a 3<SUB>10</SUB>-helix are seen in the central segment. The C-terminus residues, Ala(6) and Leu(7) are expended, while Val(5) is considerably distorted from a helical conformation. Two isopropanol molecules make hydrogen bonds to the C-terminal segment, while a water molecule interacts with the N-terminus. The structure is in contrast to that obtained for the same peptide in crystals from methanol-water [ I. L. Karle, J. L. Flippen-Anderson, K. Uma, and P. Balaram (1990) Proteins: Structure, Function and Genetics, Vol. 7, pp. 62-73] in which two independent molecules reveal an almost perfect α-helix and a helix penetrated by a water molecule. A comparison of the three structures provides a snapshot of the progressive effects of solvation leading to helix unwinding. The fragility of the heptapeptide helix in solution is demonstrated by nmr studies in CDC1<SUB>3</SUB> and (CD<SUB>3</SUB>)<SUB>2</SUB>SO. A helical conformation is supported in the apolar solvent CDCl<SUB>3</SUB>, whereas almost complete unfolding is observed in the strongly solvating medium (CD<SUB>3</SUB>)<SUB>2</SUB>SO