title: Determination of the X-ray structure of the snake venom protein omwaprin by total chemical synthesis and racemic protein crystallography.
abstract: The 50-residue snake venom protein L-omwaprin and its enantiomer D-omwaprin were prepared by total chemical synthesis. Radial diffusion assays were performed against Bacillus megaterium and Bacillus anthracis; both L- and D-omwaprin showed antibacterial activity against B. megaterium. The native protein enantiomer, made of L-amino acids, failed to crystallize readily. However, when a racemic mixture containing equal amounts of L- and D-omwaprin was used, diffraction quality crystals were obtained. The racemic protein sample crystallized in the centrosymmetric space group P2(1)/c and its structure was determined at atomic resolution (1.33 A) by a combination of Patterson and direct methods based on the strong scattering from the sulfur atoms in the eight cysteine residues per protein. Racemic crystallography once again proved to be a valuable method for obtaining crystals of recalcitrant proteins and for determining high-resolution X-ray structures by direct methods.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Banigan
authors.forename: Kalyaneswar
authors.initials: K
authors.lastname: Mandal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sawaya
authors.forename: Vilasak
authors.initials: V
authors.lastname: Thammavongsa
authors.forename: Antoni P A
authors.initials: AP
authors.lastname: Hendrickx
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.forename: Todd O
authors.initials: TO
authors.lastname: Yeates
authors.forename: Stephen B H
authors.initials: SB
authors.lastname: Kent
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D001410:Bacillus megaterium / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004546:Elapid Venoms / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013058:Mass Spectrometry; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013237:Stereoisomerism
chemical_list: D023181:Antimicrobial Cationic Peptides; D004546:Elapid Venoms; C517856:omwaprin protein, Oxyuranus microlepidotus