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1.  Structure of the cytoplasmic domain of Yersinia pestis YscD, an essential component of the type III secretion system 
The crystal structure of the cytoplasmic domain of Y. pestis YscD is presented at 2.04 Å resolution.
The Yersinia pestis YscD protein is an essential component of the type III secretion system. YscD consists of an N-terminal cytoplasmic domain (residues 1–121), a transmembrane linker (122–142) and a large periplasmic domain (143–419). Both the cytoplasmic and the periplasmic domains are required for the assembly of the type III secretion system. Here, the structure of the YscD cytoplasmic domain solved by SAD phasing is presented. Although the three-dimensional structure is similar to those of forkhead-associated (FHA) domains, comparison with the structures of canonical FHA domains revealed that the cytoplasmic domain of YscD lacks the conserved residues that are required for binding phosphothreonine and is therefore unlikely to function as a true FHA domain.
doi:10.1107/S0907444911054308
PMCID: PMC3282619  PMID: 22349221
YscD; Yersinia pestis; type III secretion systems; cytoplasmic domain
2.  Isothiazolidinone (IZD) as a phosphoryl mimetic in inhibitors of the Yersinia pestis protein tyrosine phosphatase YopH 
The first X-ray crystal structure of the Y. pestis protein tyrosine phosphatase YopH in complex with an isothiazolidinone-based lead-fragment compound is reported.
Isothiazolidinone (IZD) heterocycles can act as effective components of protein tyrosine phosphatase (PTP) inhibitors by simultaneously replicating the binding interactions of both a phosphoryl group and a highly conserved water molecule, as exemplified by the structures of several PTP1B–inhibitor complexes. In the first unambiguous demonstration of IZD interactions with a PTP other than PTP1B, it is shown by X-ray crystallography that the IZD motif binds within the catalytic site of the Yersinia pestis PTP YopH by similarly displacing a highly conserved water molecule. It is also shown that IZD-based bidentate ligands can inhibit YopH in a nonpromiscuous fashion at low micromolar concentrations. Hence, the IZD moiety may represent a useful starting point for the development of YopH inhibitors.
doi:10.1107/S0907444911018610
PMCID: PMC3121299  PMID: 21697602
YopH; isothiazolidinone; Yersinia pestis; protein tyrosine phosphatases
3.  Structure of human dual-specificity phosphatase 27 at 2.38 Å resolution 
The X-ray crystal structure of human dual-specificity phosphatase 27 (DUSP27) is reported at 2.38 Å resolution.
There are over 100 genes in the human genome that encode protein tyrosine phosphatases (PTPs) and approximately 60 of these are classified as dual-specificity phosphatases (DUSPs). Although many dual-specificity phosphatases are still not well characterized, novel functions have been discovered for some of them that have led to new insights into a variety of biological processes and the molecular basis for certain diseases. Indeed, as the functions of DUSPs continue to be elucidated, a growing number of them are emerging as potential therapeutic targets for diseases such as cancer, diabetes and inflammatory disorders. Here, the overexpression, purification and structure determination of DUSP27 at 2.38 Å resolution are presented.
doi:10.1107/S090744491100970X
PMCID: PMC3087626  PMID: 21543850
dual-specificity phosphatases; DUSP27; protein tyrosine phosphatases
4.  Overproduction, purification and structure determination of human dual-specificity phosphatase 14 
The crystal structure of human dual-specificity phosphatase 14, DUSP14 (MKP6), in complex with a phosphate ion has been determined and refined to 1.88 Å resolution.
Dual-specificity phosphatases (DUSPs) are enzymes that participate in the regulation of biological processes such as cell growth, differentiation, transcription and metabolism. A number of DUSPs are able to dephosphorylate phosphoryl­ated serine, threonine and tyrosine residues on mitogen-activated protein kinases (MAPKs) and thus are also classified as MAPK phosphatases (MKPs). As an increasing number of DUSPs are being identified and characterized, there is a growing need to understand their biological activities at the molecular level. There is also significant interest in identifying DUSPs that could be potential targets for drugs that modulate MAPK-dependent signaling and immune responses, which have been implicated in a variety of maladies including cancer, infectious diseases and inflammatory disorders. Here, the overproduction, purification and crystal structure at 1.88 Å resolution of human dual-specificity phosphatase 14, DUSP14 (MKP6), are reported. This structural information should accelerate the study of DUSP14 at the molecular level and may also accelerate the discovery and development of novel therapeutic agents.
doi:10.1107/S0907444909023762
PMCID: PMC2748964  PMID: 19770498
dual-specificity phosphatases; MAPK phosphatases; DUSP14; MKP6

Results 1-4 (4)