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Ribose-5-phosphate isomerase (Rpi; EC 5.3.1.6) is a key activity of the pen-tose phosphate pathway. Two unrelated types of sequence⁄structure possess this activity: type A Rpi (present in most organisms) and type B Rpi (RpiB) (in some bacteria and parasitic protozoa). | IFEBS Journal Structures of type B ribose 5-phosphate isomerase from Trypanosoma cruzi shed light on the determinants of sugar specificity in the structural family Ana L. Stern1 Agata Naworyta1 Juan J. Cazzulo2 and Sherry L. Mowbray1 3 1 Department of Molecular Biology Swedish University of AgriculturalSciences Uppsala Sweden 2 Instituto de Investigaciones Biotecnologicas-Instituto Tecnologico de Chascomus IIB-INTECH Universidad Nacionalde GeneralSan Martin-CONICET Buenos Aires Argentina 3 Department of Celland Molecular Biology Uppsala University Sweden Keywords Chagas disease enzyme specificity pentose phosphate pathway type B ribose 5-phosphate isomerase RpiB X-ray crystallography Correspondence S. Mowbray Department of Molecular Biology Box 590 BiomedicalCenter SE-751 24 Uppsala Sweden Fax 46 18 53 69 71 Tel 46 18 471 4990 E-mail mowbray@xray.bmc.uu.se These authors contributed equally to this work Received 13 November 2010 revised 17 December 2010 accepted 23 December 2010 doi 10.1111 j.1742-4658.2010.07999.x Ribose-5-phosphate isomerase Rpi EC 5.3.1.6 is a key activity of the pentose phosphate pathway. Two unrelated types of sequence structure possess this activity type A Rpi present in most organisms and type B Rpi RpiB in some bacteria and parasitic protozoa . In the present study we report enzyme kinetics and crystallographic studies of the RpiB from the human pathogen Trypanosoma cruzi. Structures of the wild-type and a Cys69Ala mutant enzyme alone or bound to phosphate D-ribose 5-phosphate or the inhibitors 4-phospho-D-erythronohydroxamic acid and D-allose 6-phosphate highlight features of the active site and show that small conformational changes are linked to binding. Kinetic studies confirm that similar to the RpiB from Mycobacterium tuberculosis the T. cruzi enzyme can isomerize D-ribose 5-phosphate effectively but not the 6-carbon sugar D-allose 6-phos-phate instead this sugar acts as an inhibitor of both enzymes. The behaviour is distinct from that
