Tm_Cel5A, which belongs to family 5 of the glycoside hydrolases, is an extremely stable enzyme among the endo-acting glycosidases present in the hyperthermophilic organism Therrnotoga maritima. Members of GH5 family shows a common (beta/alpha)(8) TIM-barrel fold in which the catalytic acid/base and nucleophile are located on strands beta-4 and beta-7 of the barrel fold. Thermally resistant cellulases are desirable for lignocellulosic biofuels production and the Tm_Cel5A is an excellent candidate for use in the degradation of polysaccharides present on biomass. This paper describes two Tm_Cel5A structures (crystal forms I and II) solved at 2.20 and 1.85 angstrom resolution, respectively. Our analyses of the Tm_Cel5A structure and comparison to a mesophilic GH5 provides a basis for the thermostability associated with Tm_Cel5A. Furthermore, both crystal forms of Tm_Cel5A possess a cadmium (Cd2+) ion bound between the two catalytic residues. Activity assays of Tm_Cel5A confirmed a strong inhibition effect in the presence of Cd2+ metal ions demonstrating competition with the natural substrate for the active site. Based on the structural information we have obtained for Tm_Cel5A, protein bioengineering can be used to potentially increase the thermostability of mesophilic cellulase enzymes. Published by Elsevier Inc.