Cole, K.

Kotz, J.

Kubasik, Matthew A.

Placido, J.

English

Fairfield University: DigitalCommons@Fairfield

Fairfield University DigitalCommons@Fairfield Chemistry & Biochemistry Faculty Publications Chemistry & Biochemistry Department 2-2003 Conformational Dynamics of Short C-13-Labeled Helical Peptides as Measured by Dynamic NMR Spectroscopy Matthew A. Kubasik Fairfield University, mkubasik@fairfield.edu K. Cole J. Kotz J. Placido Follow this and additional works at: https://digitalcommons.fairfield.edu/chemistry-facultypubs © 2003 by the Biophysical Society Peer Reviewed Repository Citation Kubasik, Matthew A.; Cole, K.; Kotz, J.; and Placido, J., "Conformational Dynamics of Short C-13-Labeled Helical Peptides as Measured by Dynamic NMR Spectroscopy" (2003). Chemistry & Biochemistry Faculty Publications. 1. https://digitalcommons.fairfield.edu/chemistry-facultypubs/1 Published Citation Kubasik, M. A.; Cole, K.; Kotz, J.; Placido, J. Conformational Dynamics of Short C-13-Labeled Helical Peptides as Measured by Dynamic NMR Spectroscopy. Biophys. J. 2003, 2 (Part 2, supplemental issue), 502A. This item has been accepted for inclusion in DigitalCommons@Fairfield by an authorized administrator of DigitalCommons@Fairfield. It is brought to you by DigitalCommons@Fairfield with permission from the rights-holder(s) and is protected by copyright and/or related rights. You are free to use this item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses, you need to obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/or on the work itself. For more information, please contact digitalcommons@fairfield.edu. Wednesday PM2451-Pos Board # B49Changes in the Molar Ellipticities of HEWL Observed byCircular Dichroism and Quantitated by Time ResolvedFluorescence Anisotropy Under Crystallizing Conditions.John Paul Sumidai, Marc L Pusey2'USRA, 4950 Corporate Drive, Suite 100, Huntsville, Alabama35803, 2Office of Biological and Physical Research,NASA/Marshall Space Flight Center, Huntsville, Alabama 34812Fluid models for simple colloids predict that as the proteinconcentration is increased, crystallization should occur at somesufficiently high concentration regardless of the strength ofattraction. However, empirical measurements do not fully supportthis assertion. Measurements of the second virial coefficient (B22)indicate that protein crystallization occurs only over a discreterange of solution parameters. Furthermore, observations of astrong correlation between protein solubility and B22, has led to anongoing debate regarding the relationship between the two.Experimental work in our lab, using Hen Egg White Lysozyme(HEWL), previously revealed that the rotational anisotropy of theprotein under crystallizing conditions changes systematically withpH, ionic strength and temperature. These observations are nowsupported by recent work revealing that small changes in the molarellipticity also occur systematically with changes in ionic strengthand temperature. This work demonstrates that undercrystallization conditions, the protein native state is characterizedby a conformational heterogeneity that may prove fundamental tothe relationship between protein crystallization and proteinsolubility.2452-Pos Board # B50Conformational Dynamics of Short 13C-labeled HelicalPeptides as Measured by Dynamic NMR SpectroscopyMatthew A. Kubasikl, Kathryn Cole', James Kotzl, JessicaPlacidol'Fairfield University, 1073 N. Benson Rd, Fairfield, Connecticut06824The helix is the most common secondary structural motif inproteins, and it continues to attract much theoretical andexperimental interest. We are using oligomers of the stronglyhelix forming residue ax-aminoisobutyric acid (AIB) as models ofhelical structure and dynamics. Oligomers of this achiral residueare known to form left- and right-handed 3 lo helices. The rates ofinterconversion between enantiomeric left- and right-handedhelices can be measured using dynamic NMR techniques (Hummelet al., Angew. Chem. Int. Ed. 26, 1150 (1987)). We havesynthesized hexameric and octameric oligomers of AIB, each 13C-labeled at a single residue. Using lineshape analysis of the labeled13C residues, we have measured the enantiomerization kinetics forthese organic-soluble peptides in CD2Cl2. Within the assumptionof a fully cooperative enantiomerization transition, the octamer andhexamer show a similar AHt of around 30 kJ/mol. However, theoctamer has a larger, more negative AS" than the hexamer. Thethermodynamic activation parameters for the conformationalenantiomerization dynamics of these peptides will be discussed.2453-Pos Board # B51Homology Modeling of Myson Light Chain Kinase forStructure Based Drug Design.Armen Nalian', Beatrice A Clack''Stephen F. Austin State Univ., P.O. Box 6132, SFA Station,Nacogdoches, Texas 75962Myosin Light Chain Kinase (MLCK) is a regulatory enzyme insmooth and skeletal muscle contraction. MLCK has been shownto be involved in invasion and metastasis of pancreatic cancer andglioma along with bronchial diseases. Identification of specificinhibitors may offer a therapeutic strategy for preventing theproliferation of certain cancers and diseases. In this study, wehave built a model of the smooth and skeletal MLCK's catalyticcore and regulatory domain based on recently available crystalstructures of the Death-associated Protein Kinase (DAPK),Twitchen Kinase and Titan using the Accelrys, Inc. softwareInsight II HOMOLOGY. The percent identity between thecatalytic cores of these enzymes and smooth and skeletal MLCK isa minimum of 47% as opposed to 31% with the cAMP-dependentprotein kinase catalytic core used for modeling of smooth MLCKby Knighton et.al (1992). We believe that the new model is morereliable and a more accurate representation of MLCK and thereforecan be used for structure-based design of specific smooth andskeletal MLCK inhibitors. In addition, the new models offer newstrategies for further experiments that will give insight into themolecular bases of substrate specificity between smooth andskeletal MLCK.2454-Pos Board # B52A highly conserved arginine is critical for the functionalfolding of Inhibitor of Apoptosis (IAP) BIR domainsLaura E Luquel, Katrina P Grape', Matthew Junkerl'University of Texas at Dallas, 2601 North Floyd Road,Richardson, Texas 75080The Inhibitor of Apoptosis (IAP) proteins are found in all animalsand regulate apoptosis (programmed cell death) by binding andinhibiting caspase proteases. This inhibition is overcome byseveral apoptosis stimulators, including Drosophila Hid andmammalian Smac/DIABLO, which bind to 65 residue BaculovirusIAP Repeat (BIR) domains found in 1-3 copies in all IAPs.Virtually all BIRs contain 3 Cys and a His that bind zinc, a Gly ina tight turn, and an Arg. The functional and structural role of theArg was investigated in isolated BIR domains from the baculovirusOrgyia pseudotsugata Op-IAP and the Drosophila DIAPIproteins. Mutation of the Arg to either Ala or Lys abolished Hidand Smac binding to BIRs, despite the Hid/Smac binding sitebeing located on the opposite side of the BIR domain from theArg. The mutant BIR domains also exhibited weakened zincbinding, increased sensitivity to limited proteolysis, and alteredcircular dichroism spectra indicative of perturbed domain folding.Examination of known BIR structures indicates that the Arg sidechain makes simultaneous bridging hydrogen bonds and a cation-Einteraction for which the Arg guanidino group is uniquely well-suited. These interactions are likely critical for stabilizing thetertiary fold of BIR domains in all IAPs, explaining theconservation of this residue.2455-Pos Board # B53Multi-resolution modeling of protein dynamics-functionrelationshipOgnjen Perisic', Turkan Haliloglu2, Hui Lu''Department of Bioengineering, University of Illinois at Chicago,851 S Morgan St., Rm 218, Chicago, Illinois 60607, 2BogaziciUniversity, Polymer Research Center, Istanbul, 80815 TurkeyProtein's function closely correlates with its dynamic behavior. Wehave used both the atomic detailed molecular dynamics and theresidue level conformation analysis to study protein dynamics nearits native conformation. In protein-protein interaction study, wehave found the residues involved in high-frequency mode correlatewith the its binding sites. This information can then be used inprotein binding site prediction and protein interaction networkprediciton. In force-induced unfolding of mechanical proteins, thelow frequency dynamic modes of the protein dramatically changedduring the key unfolding events.2456-Pos Board # B54Investigation of cooperative phase transition in elastin aqueoussolutionYanjie Zhang', Hanbin Mao', Paul S. Cremer''Texas A&M University, 3255 TAMU, College Station, Texas77843Elastin has been widely investigated for its unique properties insolution. Aqueous solutions of a-elastin, a fragmentation productfrom elastin fiber, undergo an inverse phase transition upontemperature increase. In this presentation, the phase transition of502a2451-2456 POSTERS

Conformational Dynamics of Short C-13-Labeled Helical Peptides as Measured by Dynamic NMR Spectroscopy

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Conformational Dynamics of Short C-13-Labeled Helical Peptides as Measured by Dynamic NMR Spectroscopy

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