A new structural class of serine protease inhibitors revealed by the structure of the hirustasin–kallikrein complex

AbstractBackground: Hirustasin belongs to a class of serine protease inhibitors characterized by a well conserved pattern of cysteine residues. Unlike the closely related inhibitors, antistasin/ghilanten and guamerin, which are selective for coagulation factor Xa or neutrophil elastase, hirustasin binds specifically to tissue kallikrein. The conservation of the pattern of cysteine residues and the significant sequence homology suggest that these related inhibitors possess a similar three-dimensional structure to hirustasin.Results: The crystal structure of the complex between tissue kallikrein and hirustasin was analyzed at 2.4 Å resolution. Hirustasin folds into a brick-like structure that is dominated by five disulfide bridges and is sparse in secondary structural elements. The cysteine residues are connected in an abab cdecde pattern that causes the polypeptide chain to fold into two similar motifs. As a hydrophobic core is absent from hirustasin the disulfide bridges maintain the tertiary structure and present the primary binding loop to the active site of the protease. The general structural topography and disulfide connectivity of hirustasin has not previously been described.Conclusions: The crystal structure of the kallikrein–hirustasin complex reveals that hirustasin differs from other serine protease inhibitors in its conformation and its disulfide bond connectivity, making it the prototype for a new class of inhibitor. The disulfide pattern shows that the structure consists of two domains, but only the C-terminal domain interacts with the protease. The disulfide pattern of the N-terminal domain is related to the pattern found in other proteins. Kallikrein recognizes hirustasin by the formation of an antiparallel β sheet between the protease and the inhibitor. The P1 arginine binds in a deep negatively charged pocket of the enzyme. An additional pocket at the periphery of the active site accommodates the sidechain of the P4 valine

Counting points on hyperelliptic curves over finite fields

International audienceWe describe some algorithms for computing the cardinality of hyperelliptic curves and their Jacobians over finite fields. They include several methods for obtaining the result modulo small primes and prime powers, in particular an algorithm à la Schoof for genus 2 using Cantor's division polynomials. These are combined with a birthday paradox algorithm to calculate the cardinality. Our methods are practical and we give actual results computed using our current implementation. The Jacobian groups we handle are larger than those previously reported in the literature

A heuristic quasi-polynomial algorithm for discrete logarithm in finite fields of small characteristic

International audienceIn the present work, we present a new discrete logarithm algorithm, in the same vein as in recent works by Joux, using an asymptotically more efficient descent approach. The main result gives a quasi-polynomial heuristic complexity for the discrete logarithm problem in finite field of small characteristic. By quasi-polynomial, we mean a complexity of type $n^{O(\log n)}$ where $n$ is the bit-size of the cardinality of the finite field. Such a complexity is smaller than any $L(\varepsilon)$ for $\epsilon>0$. It remains super-polynomial in the size of the input, but offers a major asymptotic improvement compared to $L(1/4+o(1))$

Secure and scalable deduplication of horizontally partitioned health data for privacy-preserving distributed statistical computation

Background Techniques have been developed to compute statistics on distributed datasets without revealing private information except the statistical results. However, duplicate records in a distributed dataset may lead to incorrect statistical results. Therefore, to increase the accuracy of the statistical analysis of a distributed dataset, secure deduplication is an important preprocessing step. Methods We designed a secure protocol for the deduplication of horizontally partitioned datasets with deterministic record linkage algorithms. We provided a formal security analysis of the protocol in the presence of semi-honest adversaries. The protocol was implemented and deployed across three microbiology laboratories located in Norway, and we ran experiments on the datasets in which the number of records for each laboratory varied. Experiments were also performed on simulated microbiology datasets and data custodians connected through a local area network. Results The security analysis demonstrated that the protocol protects the privacy of individuals and data custodians under a semi-honest adversarial model. More precisely, the protocol remains secure with the collusion of up to N − 2 corrupt data custodians. The total runtime for the protocol scales linearly with the addition of data custodians and records. One million simulated records distributed across 20 data custodians were deduplicated within 45 s. The experimental results showed that the protocol is more efficient and scalable than previous protocols for the same problem. Conclusions The proposed deduplication protocol is efficient and scalable for practical uses while protecting the privacy of patients and data custodians

Tight Reductions for Diffie-Hellman Variants in the Algebraic Group Model

Fuchsbauer, Kiltz, and Loss~(Crypto\u2718) gave a simple and clean definition of an ¥emph{algebraic group model~(AGM)} that lies in between the standard model and the generic group model~(GGM). Specifically, an algebraic adversary is able to exploit group-specific structures as the standard model while the AGM successfully provides meaningful hardness results as the GGM. As an application of the AGM, they show a tight computational equivalence between the computing Diffie-Hellman~(CDH) assumption and the discrete logarithm~(DL) assumption. For the purpose, they used the square Diffie-Hellman assumption as a bridge, i.e., they first proved the equivalence between the DL assumption and the square Diffie-Hellman assumption, then used the known equivalence between the square Diffie-Hellman assumption and the CDH assumption. In this paper, we provide an alternative proof that directly shows the tight equivalence between the DL assumption and the CDH assumption. The crucial benefit of the direct reduction is that we can easily extend the approach to variants of the CDH assumption, e.g., the bilinear Diffie-Hellman assumption. Indeed, we show several tight computational equivalences and discuss applicabilities of our techniques

Cyclic AMP and fructose-2,6-bisphosphate stimulated in vitro phosphorylation of yeast fructose-1,6-bisphosphatase.

Phosphorylation of purified yeast fructose-1,6-bisphosphatase was studied using purified preparations from yeast of two different cyclic AMP-independent protein kinases and a cyclic AMP-dependent protein kinase. Incorporation of 32P into fructose-1,6-bisphosphatase could be demonstrated only with the cyclic AMP-dependent protein kinase. Phosphorylation of fructose-1,6-bisphosphatase was stimulated by 3 μM fructose-2,6-bisphosphate and inhibited by 1 mM 5′-AMP