STRUCTURE OF EQUINE INFECTIOUS ANEMIA VIRUS PROTEINASE COMPLEXED WITH AN INHIBITOR. Jukka Kervinen (1), Alla Gustchina (1), David Powell (2), Alexander Zdanov (1), John Kay (2), and Alexander Wlodawer (1), (1) Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, MD 21702, USA, (2) University of Wales, Cardiff, Wales, UK

Equine infectious anemia virus (EIAV) belongs to the lentiviral family of retroviruses and it is a causative agent of an infectious anemia (swamp fever) in horses. EIAV proteinase (PR) processes viral polyproteins into functional molecules. X-ray structure of a complex of recombinant EIAV PR with the inhibitor HBY-793 has been solved at 1.8 Å resolution and refined to a crystallographic R-factor of 0.136. The overall fold of EIAV PR is very similar to the fold of other retroviral proteinases. However, the appearance of the second [[alpha]]-helix in the monomer is a feature not previously reported for retroviral PRs. Despite their strong structural homology, different retroviral PRs show extreme diversity in the binding of substrates and inhibitors. The diversity in affinity may be explained by the structural differences caused by sequence diversity at critical positions in the active site cleft and nearby regions. Here, comparison of the high resolution structures of EIAV PR, feline immunodeficiency virus PR, HIV PR, and Rous sarcoma virus PR are used to explain some of those differences.