D(n)-symmetrical tertiary templates for the design of tubular proteins.

Antiparallel helical bundles are found in a wide range of proteins. Often, four-helical bundles form tube-like structures, with binding sites for substrates or cofactors near their centers. For example, a transmembrane four-helical bundle in cytochrome bc(1) binds a pair of porphyrins in an elongated central cavity running down the center of the structure. Antiparallel helical barrels with larger diameters are found in the crystal structures of TolC and DSD, which form antiparallel 12-helical and six-helical bundles, respectively. The backbone geometries of the helical bundles of cytochrome bc(1), TolC, and DSD are well described using a simple D(n)-symmetrical model with only eight adjustable parameters. This parameterization provides an excellent starting point for construction of minimal models of these proteins as well as the de novo design of proteins with novel functions.

Potential of increased risk of neurovascular injury using proximal interlocking screws of retrograde femoral nails in patients with acetabular fractures.

OBJECTIVES: Neurologic and vascular structures are at risk of iatrogenic injury from proximal interlocking screw insertion after retrograde nailing. This risk may increase in the presence of acetabular fractures because of the displacement of soft tissues resulting from hematoma. The purpose of this study was to establish and compare the relative safe zones (RSZs) for interlocking screw insertion in adults with and without concomitant acetabular fractures. MATERIALS AND METHODS: Thirty pelvic computed tomography scans of patients with acute unilateral acetabular fracture and magnetic resonance imaging scans of five healthy legs were used to evaluate the course of the femoral sheath, neurovascular complex, and the sciatic nerve as they course through the proximal thigh in sixty-five limbs. RESULTS: The anatomy of the neurovascular structures on the fractured side was statistically different from that of the normal side. On the normal side, the RSZ at the lesser trochanteric level was identified from +7 degrees medial to +20 degrees lateral to the sagittal axis (27-degree angle zone) for anteroposterior screw placement. These values for the fractured side, respectively, changed to +1 degrees and +14 degrees (13-degree angle zone), a 52 percent decrease. The RSZ for lateral-medial screw placement was 28 degrees anterior to 39 degrees posterior to the coronal axis (67-degree angle zone) for the normal side, which changed, respectively, to 32 degrees and 41 degrees (73-degree angle zone) for the fractured side. At the level of the lesser trochanter, rotation in the femoral shaft was mimicked only in part (approximately 50 percent) by the neurovascular structures. CONCLUSION: Lateral-medial screw insertion is safer than anteroposterior insertion. Anteroposterior screw insertion becomes even more critical if the acetabulum is fractured. Femoral external rotation after rod insertion, but before screw insertion, will enlarge the safe zones.

Retrostructural analysis of metalloproteins: application to the design of a minimal model for diiron proteins.

De novo protein design provides an attractive approach for the construction of models to probe the features required for function of complex metalloproteins. The metal-binding sites of many metalloproteins lie between multiple elements of secondary structure, inviting a retrostructural approach to constructing minimal models of their active sites. The backbone geometries comprising the metal-binding sites of zinc fingers, diiron proteins, and rubredoxins may be described to within approximately 1 A rms deviation by using a simple geometric model with only six adjustable parameters. These geometric models provide excellent starting points for the design of metalloproteins, as illustrated in the construction of Due Ferro 1 (DF1), a minimal model for the Glu-Xxx-Xxx-His class of dinuclear metalloproteins. This protein was synthesized and structurally characterized as the di-Zn(II) complex by x-ray crystallography, by using data that extend to 2.5 A. This four-helix bundle protein is comprised of two noncovalently associated helix-loop-helix motifs. The dinuclear center is formed by two bridging Glu and two chelating Glu side chains, as well as two monodentate His ligands. The primary ligands are mostly buried in the protein interior, and their geometries are stabilized by a network of hydrogen bonds to second-shell ligands. In particular, a Tyr residue forms a hydrogen bond to a chelating Glu ligand, similar to a motif found in the diiron-containing R2 subunit of Escherichia coli ribonucleotide reductase and the ferritins. DF1 also binds cobalt and iron ions and should provide an attractive model for a variety of diiron proteins that use oxygen for processes including iron storage, radical formation, and hydrocarbon oxidation.

Tertiary templates for the design of diiron proteins.

Diiron proteins represent a diverse class of structures involved in the binding and activation of oxygen. This review explores the simple structural features underlying the common metal-ion-binding and oxygen-binding properties of these proteins. The backbone geometries of their active sites are formed by four-helix bundles, which may be parameterized to within approximately 1 A root mean square deviation. Such parametric models are excellent starting points for investigating how asymmetric deviations from an idealized geometry influence the functional properties of the metal ion centers. These idealized models also provide attractive frameworks for de novo protein design.

De novo design and structural characterization of proteins and metalloproteins.

De novo protein design has recently emerged as an attractive approach for studying the structure and function of proteins. This approach critically tests our understanding of the principles of protein folding; only in de novo design must one truly confront the issue of how to specify a protein's fold and function. If we truly understand proteins, it should be possible to design receptors, enzymes, and ion channels from scratch. Further, as this understanding evolves and is further refined, it should be possible to design proteins and biomimetic polymers with properties unprecedented in nature.

Reconstruction of chronic rupture of the extensor mechanism after patellectomy.

Chronic extensor mechanism ruptures are uncommon but challenging clinical problems. Previously published procedures for treating chronic extensor mechanism ruptures assume an intact patella is available to anchor the repair. A case is presented of a patient who had a previous patellectomy, followed by rupture of the extensor mechanism. After two failed attempts at repair, an Achilles tendon allograft was used successfully to restore function of the extensor mechanism. The described technique offers an alternative for reconstruction of the extensor mechanism after patellectomy.

[Tyrosinosis. A difficult diagnosis of late infancy]. / Tirosinosi. Una diagnosi difficile nella seconda infanzia.

The Authors report an unusual case of tyrosinosis in which neonatal metabolic screenings were not performed and the diagnosis was made only at 4 years of age. The diet induced an improvement of cirrhosis but did not influence renal tubular damage. The authors stress the diagnostic differential elements against other cirrhogenic metabolic diseases and emphasize the prospectives of liver transplantation.