Three-Dimensional Structures and Mechanisms of Snake Venom Serine Proteinases, Metalloproteinases, and Phospholipase A 2 s M. A. Coronado a , F. R. de Moraes a , A. Ullah a , R. Masood a , V. S. Santana a , R. Mariutti a , H. Brognaro a , D. Georgieva b , M. T. Murakami c , C. Betzel b and R. K. Arni a * a Department of Physics, IBILCE/UNESP, Multi User Center for Biomolecular Innovation, São Jose do Rio Preto-SP, Brazil b Institute of Biochemistry and Molecular Biology, University of Hamburg, Laboratory of Structural Biology of Infection and Inflammation, c/o DESY, Hamburg, Germany c National Laboratory for Biosciences, National Center for Research in Energy and Materials, Campinas, Brazil Abstract High-resolution crystal structures provide accurate information of the positions of the atoms which can be used to understand substrate specificity, secondary binding sites, and catalytic mechanisms. Detailed structural information and mechanisms of serine proteinases, metalloproteinases, and phospholipases A2s are presented. Introduction Structural information gleaned at the molecular and atomic levels, when correlated with biochemical and biophysical details capable of generating a coherent picture of the salient structural features and interactions that modulate and determine biomolecular recognition, specificity, and hydrolysis, provides us with very powerful tools to decipher, step-by-step, complex biological phenomena, thus permitting a profound understanding of the basic underlying role of molecular architectural diversity in efficiently performing essential, distinct, chemical reactions that are central to life. The enormous number of protein and DNA sequences currently deposited in the data banks (e.g., http://www.expasy.org, http://www.uniprot.org) indicate that the one-dimensional representation of protein sequences generally contains a trace of the fingerprint of evolution, and often, only a faint residual of the ancestral protein is retained in the protein linear amino acid sequence. However, upon closer examination, the application of this concept exposes its fundamental limitations, and hence, its utility is strictly limited since (a) proteins that perform the same function or catalyze similar reactions often share only very low-sequence identity, (b) proteins that are about 20 % identical in their primary sequences may still catalyze distinct reactions and modulate different functions, and (c) point mutations in the active sites or cofactor-binding sites often produce proteins that catalyze different reactions or in extreme cases result in enzymatically inactive proteins. A fundamental conceptual bridge linking the linear protein sequence and its primary biological function is encoded in the three-dimensional fold or, in other words, in the exact positions of the atoms of the protein in three dimensions. Central to this concept is the fact that the three-dimensional (3D) structure of a protein is more highly conserved during evolution (Bajaj and Blundell 1984; Finkelstein and Ptitsyn 1987) than the linear amino acid sequence of the protein, and consequently, the shape of a protein, the spatial distribution of its atoms, and the surface charge, solvent *Email: arni@sjrp.unesp.br Toxinology DOI 10.1007/978-94-007-6649-5_17-3 # Springer Science+Business Media Dordrecht 2014 Page 1 of 25