PROTEIN tyrosine phosphorylation and dephosphorylation are central reactions for control of cellular division, differentiation and development1. Here we describe the crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase (PTPase)2, a cytosolic phosphatase present in many mammalian cells. The enzyme catalyses the dephosphorylation of phosphotyrosine-containing substrates3-6, and overexpression of the protein in nor-mal and transformed cells inhibits cell proliferation7,8. The structure of the low-molecular-weight PTPase reveals an a/β protein containing a phosphate-binding loop motif at the amino end of helix al. This motif includes the essential active-site residues Cys 12 and Arg 18 and bears striking similarities to the activesite motif recently described in the structure of human PTP1B9. The structure of the low-molecular-weight PTPase supports a reaction mechanism involving the conserved Cys 12 as an attacking nucleophile in an in-line associative mechanism. The structure also suggests a catalytic role for Asp 129 in the reaction cycle.

Structural genomics efforts at the Chinese Academy of Sciences and Peking University are reported in this article. The major targets for the structural genomics project are targeted proteins expressed in human hematopoietic stem/progenitor cells, proteins related to blood diseases and other human proteins. Up to now 328 target genes have been constructed in expression vectors. Among them, more than 50% genes have been expressed in Escherichia coli, approximately 25% of the resulting proteins are soluble, and 35 proteins have been purified. Crystallization, data collection and structure determination are continuing. Experiences accumulated during this initial stage are useful for designing and applying high-throughput approaches in structural genomics.

Native and His-tagged mutant (L160I) hypoxanthine-guanine phosphoribosyltransferase (HGPRT) from Thermoanaerobacter tengcongensis were cloned, expressed in Escherichia coli and purified. Both proteins were crystallized with polyethylene glycol as the main precipitant at 293 Kusing the hanging-drop vapour-diffusion method. The crystal of native HGPRT belongs to space group C2221, with unit-cell parameters a=65.77, b=137.73, c=95.27 A

Hemolin, an insect immunoglobulin superfamily member, is a lipopolysaccharide-binding immune protein induced during bacterial infection. The 3.1 angstrom crystal structure reveals a bound phosphate and patches of positive charge, which may represent the lipopolysaccharide binding site, and a new and unexpected arrangement of four immunoglobulin-like domains forming a horseshoe. Sequence analysis and analytical ultracentrifugation suggest that the domain arrangement is a feature of the L1 family of neural cell adhesion molecules related to hemolin. These results are relevant to interpretation of human L1 mutations in neurological diseases and suggest a domain swapping model for how L1 family proteins mediate homophilic adhesion.