Rethinking Patent Fraud Enforcement in a Reform Era

This Article contends that, while the defense of inequitable conduct offers an avenue to combat fraudulent patent applications, the doctrine suffers from shortcomings that spring from two compromises. First, the amorphous nature of the equitable defense prompts institutional conflict between the United States Patent and Trademark Office and the Federal Circuit. Second, by relegating enforcement solely to a patentee\u27s market competitors, the defense fails to protect the public interest adequately. In light of these compromises, the authors propose two goals to guide current reform efforts in Congress. Initially, Congress\u27s attempt to reform patent fraud enforcement should relieve the aforementioned institutional conflict. More deeply, Congress should reevaluate what overall policies should drive American patent law

Solution structure of a single-domain thiosulfate sulfurtransferase from Arabidopsis thaliana

We describe the three-dimensional structure of the product of Arabidopsis thaliana gene At5g66040.1 as determined by NMR spectroscopy. This protein is categorized as single-domain sulfurtransferase and is annotated as a senescence-associated protein (sen1-like protein) and ketoconazole resistance protein (http://arabidopsis.org/info/genefamily/STR_genefamily.html). The sequence of At5g66040.1 is virtually identical to that of a protein from Arabidopsis found by others to confer ketoconazole resistance in yeast. Comparison of the three-dimensional structure with those in the Protein Data Bank revealed that At5g66040.1 contains an additional mobile β-hairpin not found in other rhodaneses that may function in binding specific substrates. This represents the first structure of a single-domain plant sulfurtransferase. The enzymatically active cysteine-containing domain belongs to the CDC25 class of phosphatases, sulfide dehydrogenases, and stress proteins such as senescence specific protein 1 in plants, PspE and GlpE in bacteria, and cyanide and arsenate resistance proteins. Versions of this domain that lack the active site cysteine are found in other proteins, such as phosphatases, ubiquitin hydrolases, and sulfuryltransferases

Solution structure of Arabidopsis thaliana protein At5g39720.1, a member of the AIG2-like protein family

The solution structure of A. thaliana protein At5g39720.1 reported here is the first for a member of the AIG2-like family (PF06094). The three-dimensional structure shows similarity to those determined for members of the uncharacterized Pfam family UPF0131

Solution structure of human sorting nexin 22

The sorting nexins (SNXs) constitute a large group of PX domain-containing proteins that play critical roles in protein trafficking. We report here the solution structure of human sorting nexin 22 (SNX22). Although SNX22 has <30% sequence identity with any PX domain protein of known structure, it was found to contain the α/β fold and compact structural core characteristic of PX domains. Analysis of the backbone dynamics of SNX22 by NMR relaxation measurements revealed that the two walls of the ligand binding cleft undergo internal motions: on the picosecond timescale for the β1/β2 loop and on the micro- to millisecond timescale for the loop between the polyproline motif and helix α2. Regions of the SNX22 structure that differ from those of other PX domains include the loop connecting strands β1 and β2 and the loop connecting helices α1 and α2, which appear to be more mobile than corresponding loops in other known structures. The interaction of dibutanoyl-phosphatidylinositol-3-phosphate (dibutanoyl-PtdIns(3)P) with SNX22 was investigated by an NMR titration experiment, which identified the binding site in a basic cleft and indicated that ligand binding leads only to a local structural rearrangement as has been found with other PX domains. Because motions in the loops are damped out when dibutanoyl-PtdIns(3)P binds, entropic effects could contribute to the lower affinity of SNX22 for this ligand compared to other PX domains

Solution structure of thioredoxin h1 from Arabidopsis thaliana

Present in virtually every species, thioredoxins catalyze disulfide/dithiol exchange with various substrate proteins. While the human genome contains a single thioredoxin gene, plant thioredoxins are a complex protein family. A total of 19 different thioredoxin genes in six subfamilies has emerged from analysis of the Arabidopsis thaliana genome. Some function specifically in mitochondrial and chloroplast redox signaling processes, but target substrates for a group of eight thioredoxin proteins comprising the h subfamily are largely uncharacterized. In the course of a structural genomics effort directed at the recently completed A. thaliana genome, we determined the structure of thioredoxin h1 (At3g51030.1) in the oxidized state. The structure, defined by 1637 NMR-derived distance and torsion angle constraints, displays the conserved thioredoxin fold, consisting of a five-stranded β-sheet flanked by four helices. Redox-dependent chemical shift perturbations mapped primarily to the conserved WCGPC active-site sequence and other nearby residues, but distant regions of the C-terminal helix were also affected by reduction of the active-site disulfide. Comparisons of the oxidized A. thaliana thioredoxin h1 structure with an h-type thioredoxin from poplar in the reduced state revealed structural differences in the C-terminal helix but no major changes in the active site conformation