Integrative, dynamic structural biology at atomic resolution—it's about time (original) (raw)
Boehr, D.D., McElheny, D., Dyson, H.J. & Wright, P.E. The dynamic energy landscape of dihydrofolate reductase catalysis. Science313, 1638–1642 (2006). CPMG relaxation dispersion experiments characterize the structural dynamics of the catalytic cycle of DHFR as a sequence of ‘linked’ ground and excited states. ArticleCASPubMed Google Scholar
Henzler-Wildman, K.A. et al. Intrinsic motions along an enzymatic reaction trajectory. Nature450, 838–844 (2007). ArticleCASPubMed Google Scholar
Fleishman, S.J. et al. Computational design of proteins targeting the conserved stem region of influenza hemagglutinin. Science332, 816–821 (2011). ArticleCASPubMedPubMed Central Google Scholar
Whitehead, T.A. et al. Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing. Nat. Biotechnol.30, 543–548 (2012). ArticleCASPubMedPubMed Central Google Scholar
Linder, M., Johansson, A.J., Olsson, T.S.G., Liebeschuetz, J. & Brinck, T. Computational design of a Diels-Alderase from a thermophilic esterase: the importance of dynamics. J. Comput. Aided Mol. Des.26, 1079–1095 (2012). ArticleCASPubMed Google Scholar
Volkov, A.N., Worrall, J.A.R., Holtzmann, E. & Ubbink, M. Solution structure and dynamics of the complex between cytochrome c and cytochrome c peroxidase determined by paramagnetic NMR. Proc. Natl. Acad. Sci. USA103, 18945–18950 (2006). ArticleCASPubMedPubMed Central Google Scholar
Tang, C., Iwahara, J. & Clore, G.M. Visualization of transient encounter complexes in protein-protein association. Nature444, 383–386 (2006). ArticleCASPubMed Google Scholar
van den Bedem, H., Bhabha, G., Yang, K., Wright, P.E. & Fraser, J.S. Automated identification of functional dynamic contact networks from X-ray crystallography. Nat. Methods10, 896–902 (2013). This study identifies networks of coordinated motion directly from room-temperature X-ray crystallography data, which rationalize NMR data. ArticleCASPubMedPubMed Central Google Scholar
Halabi, N., Rivoire, O., Leibler, S. & Ranganathan, R. Protein sectors: evolutionary units of three-dimensional structure. Cell138, 774–786 (2009). ArticleCASPubMedPubMed Central Google Scholar
McLaughlin, R.N. Jr., Poelwijk, F.J., Raman, A., Gosal, W.S. & Ranganathan, R. The spatial architecture of protein function and adaptation. Nature491, 138–142 (2012). This study identifies functional networks of coevolving amino acids from statistical coupling analysis, rationalized by deep mutational scanning. ArticleCASPubMedPubMed Central Google Scholar
Bhabha, G. et al. Divergent evolution of protein conformational dynamics in dihydrofolate reductase. Nat. Struct. Mol. Biol.20, 1243–1249 (2013). ArticleCASPubMedPubMed Central Google Scholar
Williamson, M.P., Havel, T.F. & Wüthrich, K. Solution conformation of proteinase inhibitor IIA from bull seminal plasma by 1H nuclear magnetic resonance and distance geometry. J. Mol. Biol.182, 295–315 (1985). ArticleCASPubMed Google Scholar
Wüthrich, K. NMR of Proteins and Nucleic Acids (Wiley, 1986).
Torda, A.E., Scheek, R.M. & van Gunsteren, W.F. Time-averaged nuclear Overhauser effect distance restraints applied to tendamistat. J. Mol. Biol.214, 223–235 (1990). ArticleCASPubMed Google Scholar
Bonvin, A.M.J.J. & Brünger, A.T. Do NOE distances contain enough information to assess the relative populations of multi-conformer structures? J. Biomol. NMR7, 72–76 (1996). ArticleCASPubMed Google Scholar
Rieping, W., Habeck, M. & Nilges, M. Inferential structure determination. Science309, 303–306 (2005). ArticleCASPubMed Google Scholar
Vögeli, B., Kazemi, S., Güntert, P. & Riek, R. Spatial elucidation of motion in proteins by ensemble-based structure calculation using exact NOEs. Nat. Struct. Mol. Biol.19, 1053–1057 (2012). ArticleCASPubMed Google Scholar
Shen, Y. et al. Consistent blind protein structure generation from NMR chemical shift data. Proc. Natl. Acad. Sci. USA105, 4685–4690 (2008). ArticlePubMedPubMed Central Google Scholar
Sripakdeevong, P. et al. Structure determination of noncanonical RNA motifs guided by 1H NMR chemical shifts. Nat. Methods11, 413–416 (2014). ArticleCASPubMedPubMed Central Google Scholar
Camilloni, C. & Vendruscolo, M. Statistical mechanics of the denatured state of a protein using replica-averaged metadynamics. J. Am. Chem. Soc.136, 8982–8991 (2014). ArticleCASPubMed Google Scholar
Fraser, J.S. et al. Accessing protein conformational ensembles using room-temperature X-ray crystallography. Proc. Natl. Acad. Sci. USA108, 16247–16252 (2011). ArticlePubMedPubMed Central Google Scholar
Hansen, D.F., Vallurupalli, P. & Kay, L.E. Using relaxation dispersion NMR spectroscopy to determine structures of excited, invisible protein states. J. Biomol. NMR41, 113–120 (2008). ArticleCASPubMed Google Scholar
Long, D. et al. A comparative CEST NMR study of slow conformational dynamics of small GTPases complexed with GTP and GTP analogues. Angew. Chem. Int. Ed. Engl.52, 10771–10774 (2013). ArticleCASPubMed Google Scholar
Bhabha, G. et al. A dynamic knockout reveals that conformational fluctuations influence the chemical step of enzyme catalysis. Science332, 234–238 (2011). ArticleCASPubMedPubMed Central Google Scholar
McElheny, D., Schnell, J.R., Lansing, J.C., Dyson, H.J. & Wright, P.E. Defining the role of active-site loop fluctuations in dihydrofolate reductase catalysis. Proc. Natl. Acad. Sci. USA102, 5032–5037 (2005). ArticleCASPubMedPubMed Central Google Scholar
Tjandra, N. & Bax, A. Direct measurement of distances and angles in biomolecules by NMR in a dilute liquid crystalline medium. Science278, 1111–1114 (1997). ArticleCASPubMed Google Scholar
Tolman, J.R., Flanagan, J.M., Kennedy, M.A. & Prestegard, J.H. NMR evidence for slow collective motions in cyanometmyoglobin. Nat. Struct. Biol.4, 292–297 (1997). ArticleCASPubMed Google Scholar
Zeng, J. et al. High-resolution protein structure determination starting with a global fold calculated from exact solutions to the RDC equations. J. Biomol. NMR45, 265–281 (2009). ArticleCASPubMedPubMed Central Google Scholar
Clore, G.M. & Schwieters, C.D. How much backbone motion in ubiquitin is required to account for dipolar coupling data measured in multiple alignment media as assessed by independent cross-validation? J. Am. Chem. Soc.126, 2923–2938 (2004). ArticleCASPubMed Google Scholar
Cavalli, A., Camilloni, C. & Vendruscolo, M. Molecular dynamics simulations with replica-averaged structural restraints generate structural ensembles according to the maximum entropy principle. J. Chem. Phys.138, 094112 (2013). ArticleCASPubMed Google Scholar
De Simone, A., Montalvao, R.W., Dobson, C.M. & Vendruscolo, M. Characterization of the interdomain motions in hen lysozyme using residual dipolar couplings as replica-averaged structural restraints in molecular dynamics simulations. Biochemistry52, 6480–6486 (2013). ArticleCASPubMed Google Scholar
Salmon, L., Bascom, G., Andricioaei, I. & Al-Hashimi, H.M. A general method for constructing atomic-resolution RNA ensembles using NMR residual dipolar couplings: the basis for interhelical motions revealed. J. Am. Chem. Soc.135, 5457–5466 (2013). ArticleCASPubMedPubMed Central Google Scholar
Emani, P.S. et al. Elucidating molecular motion through structural and dynamic filters of energy-minimized conformer ensembles. J. Phys. Chem. B118, 1726–1742 (2014). ArticleCASPubMedPubMed Central Google Scholar
Guerry, P. et al. Mapping the population of protein conformational energy sub-states from NMR dipolar couplings. Angew. Chem. Int. Ed. Engl.52, 3181–3185 (2013). ArticleCASPubMed Google Scholar
Fonseca, R., Pachov, D.V., Bernauer, J. & van den Bedem, H. Characterizing RNA ensembles from NMR data with kinematic models. Nucleic Acids Res.42, 9562–9572 (2014). ArticleCASPubMedPubMed Central Google Scholar
Berlin, K. et al. Recovering a representative conformational ensemble from underdetermined macromolecular structural data. J. Am. Chem. Soc.135, 16595–16609 (2013). ArticleCASPubMedPubMed Central Google Scholar
Lange, O.F. et al. Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution. Science320, 1471–1475 (2008). A comprehensive, integrative computational procedure reveals the conformational ensemble of ubiquition, validated by comparative crystal structure analysis. ArticleCASPubMed Google Scholar
Lipari, G. & Szabo, A. Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity. J. Am. Chem. Soc.104, 4546–4559 (1982). ArticleCAS Google Scholar
Frederick, K.K., Marlow, M.S., Valentine, K.G. & Wand, A.J. Conformational entropy in molecular recognition by proteins. Nature448, 325–329 (2007). This study establishes a linear relationship between conformational entropy and binding entropy for calmodulin. Ref.45then proposes S2axisas a proxy for binding entropy. ArticleCASPubMedPubMed Central Google Scholar
Kasinath, V., Sharp, K.A. & Wand, A.J. Microscopic insights into the NMR relaxation-based protein conformational entropy meter. J. Am. Chem. Soc.135, 15092–15100 (2013). ArticleCASPubMed Google Scholar
Tzeng, S.-R. & Kalodimos, C.G. Protein activity regulation by conformational entropy. Nature488, 236–240 (2012). ArticleCASPubMed Google Scholar
Diehl, C. et al. Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of galectin-3. J. Am. Chem. Soc.132, 14577–14589 (2010). ArticleCASPubMedPubMed Central Google Scholar
Best, R.B. & Vendruscolo, M. Determination of protein structures consistent with NMR order parameters. J. Am. Chem. Soc.126, 8090–8091 (2004). ArticleCASPubMed Google Scholar
Maragakis, P. et al. Microsecond molecular dynamics simulation shows effect of slow loop dynamics on backbone amide order parameters of proteins. J. Phys. Chem. B112, 6155–6158 (2008). ArticleCASPubMedPubMed Central Google Scholar
Showalter, S.A., Johnson, E., Rance, M. & Brüschweiler, R. Toward quantitative interpretation of methyl side-chain dynamics from NMR by molecular dynamics simulations. J. Am. Chem. Soc.129, 14146–14147 (2007). ArticleCASPubMed Google Scholar
Scouras, A.D. & Daggett, V. The Dynameomics rotamer library: amino acid side chain conformations and dynamics from comprehensive molecular dynamics simulations in water. Protein Sci.20, 341–352 (2011). ArticleCASPubMed Google Scholar
Lindorff-Larsen, K., Best, R.B., Depristo, M.A., Dobson, C.M. & Vendruscolo, M. Simultaneous determination of protein structure and dynamics. Nature433, 128–132 (2005). ArticleCASPubMed Google Scholar
Shehu, A., Clementi, C. & Kavraki, L.E. Modeling protein conformational ensembles: from missing loops to equilibrium fluctuations. Proteins65, 164–179 (2006). ArticleCASPubMed Google Scholar
Shehu, A., Kavraki, L.E. & Clementi, C. On the characterization of protein native state ensembles. Biophys. J.92, 1503–1511 (2007). ArticleCASPubMed Google Scholar
Best, R.B., Lindorff-Larsen, K., DePristo, M.A. & Vendruscolo, M. Relation between native ensembles and experimental structures of proteins. Proc. Natl. Acad. Sci. USA103, 10901–10906 (2006). ArticleCASPubMedPubMed Central Google Scholar
Cooper, A. & Dryden, D.T.F. Allostery without conformational change. A plausible model. Eur. Biophys. J.11, 103–109 (1984). A landmark study proposing that entropic changes can drive binding events. ArticleCASPubMed Google Scholar
Castellani, F. et al. Structure of a protein determined by solid-state magic-angle-spinning NMR spectroscopy. Nature420, 98–102 (2002). ArticleCASPubMed Google Scholar
Giraud, N., Bo, A., Lesage, A. & Blackledge, M. Site-specific backbone dynamics from a crystalline protein by solid-state NMR spectroscopy. J. Am. Chem. Soc.126, 11422–11423 (2004). ArticleCASPubMed Google Scholar
Zinkevich, T., Chevelkov, V., Reif, B., Saalwächter, K. & Krushelnitsky, A. Internal protein dynamics on ps to μs timescales as studied by multi-frequency 15N solid-state NMR relaxation. J. Biomol. NMR57, 219–235 (2013). ArticleCASPubMed Google Scholar
Schanda, P., Huber, M., Boisbouvier, J., Meier, B.H. & Ernst, M. Solid-state NMR measurements of asymmetric dipolar couplings provide insight into protein side-chain motion. Angew. Chem. Int. Ed. Engl.50, 11005–11009 (2011). ArticleCASPubMed Google Scholar
Haller, J.D. & Schanda, P. Amplitudes and time scales of picosecond-to-microsecond motion in proteins studied by solid-state NMR: a critical evaluation of experimental approaches and application to crystalline ubiquitin. J. Biomol. NMR57, 263–280 (2013). ArticleCASPubMedPubMed Central Google Scholar
Agarwal, V., Xue, Y., Reif, B. & Skrynnikov, N.R. Protein side-chain dynamics as observed by solution- and solid-state NMR spectroscopy: a similarity revealed. J. Am. Chem. Soc.130, 16611–16621 (2008). ArticleCASPubMed Google Scholar
Tollinger, M., Sivertsen, A.C., Meier, B.H., Ernst, M. & Schanda, P. Site-resolved measurement of microsecond-to-millisecond conformational-exchange processes in proteins by solid-state NMR spectroscopy. J. Am. Chem. Soc.134, 14800–14807 (2012). ArticleCASPubMedPubMed Central Google Scholar
Sidhu, A., Surolia, A., Robertson, A.D. & Sundd, M. A hydrogen bond regulates slow motions in ubiquitin by modulating a β-turn flip. J. Mol. Biol.411, 1037–1048 (2011). ArticleCASPubMed Google Scholar
Salvi, N., Ulzega, S., Ferrage, F. & Bodenhausen, G. Time scales of slow motions in ubiquitin explored by heteronuclear double resonance. J. Am. Chem. Soc.134, 2481–2484 (2012). ArticleCASPubMed Google Scholar
Vijay-Kumar, S., Bugg, C.E. & Cook, W.J. Structure of ubiquitin refined at 1.8 Å resolution. J. Mol. Biol.194, 531–544 (1987). ArticleCASPubMed Google Scholar
Keedy, D.A. et al. Crystal cryocooling distorts conformational heterogeneity in a model Michaelis complex of DHFR. Structure22, 899–910 (2014). ArticleCASPubMedPubMed Central Google Scholar
Rejto, P.A. & Freer, S.T. Protein conformational substates from X-ray crystallography. Prog. Biophys. Mol. Biol.66, 167–196 (1996). ArticleCASPubMed Google Scholar
Wilson, M.A. & Brunger, A.T. The 1.0 Å crystal structure of Ca2+-bound calmodulin: an analysis of disorder and implications for functionally relevant plasticity. J. Mol. Biol.301, 1237–1256 (2000). ArticleCASPubMed Google Scholar
Willis, B.T.M. & Pryor, A.W. Thermal Vibrations in Crystallography (Cambridge University Press, 1975).
Poon, B.K. et al. Normal mode refinement of anisotropic thermal parameters for a supramolecular complex at 3.42-Å crystallographic resolution. Proc. Natl. Acad. Sci. USA104, 7869–7874 (2007). ArticleCASPubMedPubMed Central Google Scholar
Schröder, G.F., Levitt, M. & Brunger, A.T. Super-resolution biomolecular crystallography with low-resolution data. Nature464, 1218–1222 (2010). ArticleCASPubMedPubMed Central Google Scholar
Schiffer, C.A., Huber, R., Wüthrich, K. & van Gunsteren, W.F. Simultaneous refinement of the structure of BPTI against NMR data measured in solution and X-ray diffraction data measured in single crystals. J. Mol. Biol.241, 588–599 (1994). ArticleCASPubMed Google Scholar
Rinaldelli, M. et al. Simultaneous use of solution NMR and X-ray data in REFMAC5 for joint refinement/detection of structural differences. Acta Crystallogr. D Biol. Crystallogr.70, 958–967 (2014). ArticleCASPubMedPubMed Central Google Scholar
Kuzmanic, A., Pannu, N.S. & Zagrovic, B. X-ray refinement significantly underestimates the level of microscopic heterogeneity in biomolecular crystals. Nat. Commun.5, 3220 (2014). ArticleCASPubMed Google Scholar
Kuriyan, J. et al. Exploration of disorder in protein structures by X-ray restrained molecular dynamics. Proteins10, 340–358 (1991). ArticleCASPubMed Google Scholar
Burling, F.T. & Brünger, A.T. Thermal motion and conformational disorder in protein crystal structures: comparison of multi-conformer and time-averaging models. Isr. J. Chem.34, 165–175 (1994). ArticleCAS Google Scholar
Levin, E.J., Kondrashov, D.A., Wesenberg, G.E. & Phillips, G.N. Jr. Ensemble refinement of protein crystal structures. Structure15, 1040–1052 (2007). ArticleCASPubMedPubMed Central Google Scholar
Rader, S.D. & Agard, D.A. Conformational substates in enzyme mechanism: the 120 K structure of α-lytic protease at 1.5 Å resolution. Protein Sci.6, 1375–1386 (1997). ArticleCASPubMedPubMed Central Google Scholar
Gros, P., van Gunsteren, W.F. & Hol, W.G. Inclusion of thermal motion in crystallographic structures by restrained molecular dynamics. Science249, 1149–1152 (1990). ArticleCASPubMed Google Scholar
Clarage, J.B. & Phillips, G.N. Cross-validation tests of time-averaged molecular dynamics refinements for determination of protein structures by X-ray crystallography. Acta Crystallogr. D Biol. Crystallogr.50, 24–36 (1994). ArticleCASPubMed Google Scholar
Burnley, B.T., Afonine, P.V., Adams, P.D. & Gros, P. Modelling dynamics in protein crystal structures by ensemble refinement. eLife1, e00311 (2012). ArticleCASPubMedPubMed Central Google Scholar
van den Bedem, H., Dhanik, A., Latombe, J.-C. & Deacon, A.M. Modeling discrete heterogeneity in X-ray diffraction data by fitting multi-conformers. Acta Crystallogr. D Biol. Crystallogr.65, 1107–1117 (2009). ArticleCASPubMedPubMed Central Google Scholar
Terwilliger, T.C. et al. Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models. Acta Crystallogr. D Biol. Crystallogr.63, 597–610 (2007). ArticleCASPubMedPubMed Central Google Scholar
Brünger, A.T. Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature355, 472–475 (1992). ArticlePubMed Google Scholar
Stenkamp, R.E. & Jensen, L.H. Resolution revisited: limit of detail in electron density maps. Acta Crystallogr. A40, 251–254 (1984). Article Google Scholar
Fenwick, R.B., van den Bedem, H., Fraser, J.S. & Wright, P.E. Integrated description of protein dynamics from room-temperature X-ray crystallography and NMR. Proc. Natl. Acad. Sci. USA111, E445–E454 (2014).This study establishes that a multiconformer crystallographic ensemble (ref.85) at room temperature accurately reflects fast dynamics in solution by relatingBfactors to NMR order parameters. ArticleCASPubMedPubMed Central Google Scholar
Brüschweiler, R. & Wright, P.E. NMR order parameters of biomolecules: a new analytical representation and application to the Gaussian axial fluctuation model. J. Am. Chem. Soc.116, 8426–8427 (1994). Article Google Scholar
Clore, G.M. & Schwieters, C.D. Concordance of residual dipolar couplings, backbone order parameters and crystallographic _B_-factors for a small α/β protein: a unified picture of high probability, fast atomic motions in proteins. J. Mol. Biol.355, 879–886 (2006). ArticleCASPubMed Google Scholar
Schneider, R. et al. Towards a robust description of intrinsic protein disorder using nuclear magnetic resonance spectroscopy. Mol. Biosyst.8, 58–68 (2012). ArticleCASPubMed Google Scholar
Krzeminski, M., Marsh, J.A., Neale, C., Choy, W.-Y. & Forman-Kay, J.D. Characterization of disordered proteins with ENSEMBLE. Bioinformatics29, 398–399 (2013). ArticleCASPubMed Google Scholar
Yang, S., Salmon, L. & Al-Hashimi, H.M. Measuring similarity between dynamic ensembles of biomolecules. Nat. Methods11, 552–554 (2014). ArticleCASPubMedPubMed Central Google Scholar
Hirata, K. et al. Determination of damage-free crystal structure of an X-ray–sensitive protein using an XFEL. Nat. Methods11, 734–736 (2014). ArticleCASPubMed Google Scholar
Acbas, G., Niessen, K.A., Snell, E.H. & Markelz, A.G. Optical measurements of long-range protein vibrations. Nat. Commun.5, 3076 (2014). ArticleCASPubMed Google Scholar
Schmidt, M. et al. Protein kinetics: structures of intermediates and reaction mechanism from time-resolved X-ray data. Proc. Natl. Acad. Sci. USA101, 4799–4804 (2004). ArticleCASPubMedPubMed Central Google Scholar
Bowman, G.R., Huang, X. & Pande, V.S. Using generalized ensemble simulations and Markov state models to identify conformational states. Methods49, 197–201 (2009). ArticleCASPubMedPubMed Central Google Scholar
Bouvignies, G. et al. Identification of slow correlated motions in proteins using residual dipolar and hydrogen-bond scalar couplings. Proc. Natl. Acad. Sci. USA102, 13885–13890 (2005). ArticleCASPubMedPubMed Central Google Scholar
Tollinger, M., Skrynnikov, N.R., Mulder, F.A., Forman-Kay, J.D. & Kay, L.E. Slow dynamics in folded and unfolded states of an SH3 domain. J. Am. Chem. Soc.123, 11341–11352 (2001). ArticleCASPubMed Google Scholar
Lang, P.T., Holton, J.M., Fraser, J.S. & Alber, T. Protein structural ensembles are revealed by redefining X-ray electron density noise. Proc. Natl. Acad. Sci. USA111, 237–242 (2014). ArticleCASPubMed Google Scholar
Eriksson, A.E. et al. Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect. Science255, 178–183 (1992). ArticleCASPubMed Google Scholar
Mulder, F.A.A., Mittermaier, A., Hon, B., Dahlquist, F.W. & Kay, L.E. Studying excited states of proteins by NMR spectroscopy. Nat. Struct. Biol.8, 932–935 (2001). ArticleCASPubMed Google Scholar
Sekhar, A. & Kay, L.E. NMR paves the way for atomic level descriptions of sparsely populated, transiently formed biomolecular conformers. Proc. Natl. Acad. Sci. USA110, 12867–12874 (2013). ArticlePubMedPubMed Central Google Scholar
Aboul-ela, F., Karn, J. & Varani, G. Structure of HIV-1 TAR RNA in the absence of ligands reveals a novel conformation of the trinucleotide bulge. Nucleic Acids Res.24, 3974–3981 (1996). ArticleCASPubMedPubMed Central Google Scholar
Kulinski, T. et al. The apical loop of the HIV-1 TAR RNA hairpin is stabilized by a cross-loop base pair. J. Biol. Chem.278, 38892–38901 (2003). ArticleCASPubMed Google Scholar
Dethoff, E.A., Petzold, K., Chugh, J., Casiano-Negroni, A. & Al-Hashimi, H.M. Visualizing transient low-populated structures of RNA. Nature491, 724–728 (2012). ArticleCASPubMedPubMed Central Google Scholar
Serrano, P. et al. Comparison of NMR and crystal structures highlights conformational isomerism in protein active sites. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun.66, 1393–1405 (2010). ArticleCASPubMedPubMed Central Google Scholar
Klock, H.E. et al. Crystal structure of a conserved hypothetical protein (gi: 13879369) from Mouse at 1.90 Å resolution reveals a new fold. Proteins61, 1132–1136 (2005). ArticleCASPubMed Google Scholar