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Christopher Davies

Title
InstitutionMedical University of South Carolina
DepartmentBiochemistry and Molecular Biology
AddressP.O. Box MSC 509
207
Drug Discovery Building - 70 President St.
Phone843-876-2302
Fax843-792-8568
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    Our group uses the technique of X-ray crystallography, as well as other biochemical approaches, to decipher the structure and function of enzymes involved in peptidoglycan synthesis in bacteria. Primarily, we study penicillin-binding proteins (PBPs), the well-known molecular targets for ß-lactam antibiotics. Mutations in these proteins are a major contributor to antibiotic resistance in bacteria and our current focus is to understand how such mutations impact the structure and kinetics of PBPs, with the goal of developing new antimicrobials that circumvent such mechanisms. Following our development of a fluorescence-polarization assay, we also conduct high-throughput screening against large chemical libraries to identify new inhibitors of PBPs for drug development. Finally, as X-ray crystallographers, we collaborate with a number of groups, both within MUSC and beyond, on various structural biology projects.
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    Biochemistry, Molecular Biology

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Turner JM, Connolly KL, Aberman KE, Fonseca JC, Singh A, Jerse AE, Nicholas RA, Davies C. Molecular Features of Cephalosporins Important for Activity against Antimicrobial-Resistant Neisseria gonorrhoeae. ACS Infect Dis. 2021 02 12; 7(2):293-308. PMID: 33533239.
      View in: PubMed
    2. Biggin AJ, Bono RK, Meduri DG, Sprain CJ, Davies CJ, Holme R, Doubrovine PV. Quantitative estimates of average geomagnetic axial dipole dominance in deep geological time. Nat Commun. 2020 11 30; 11(1):6100. PMID: 33257692.
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    3. Davies CJ, Constable CG. Rapid geomagnetic changes inferred from Earth observations and numerical simulations. Nat Commun. 2020 07 06; 11(1):3371. PMID: 32632222.
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    4. Singh A, Turner JM, Tomberg J, Fedarovich A, Unemo M, Nicholas RA, Davies C. Mutations in penicillin-binding protein 2 from cephalosporin-resistant Neisseria gonorrhoeae hinder ceftriaxone acylation by restricting protein dynamics. J Biol Chem. 2020 05 22; 295(21):7529-7543. PMID: 32253235.
      View in: PubMed
    5. Singh A, Tomberg J, Nicholas RA, Davies C. Recognition of the ß-lactam carboxylate triggers acylation of Neisseria gonorrhoeae penicillin-binding protein 2. J Biol Chem. 2019 09 20; 294(38):14020-14032. PMID: 31362987.
      View in: PubMed
    6. Lv Z, Yuan L, Atkison JH, Williams KM, Vega R, Sessions EH, Divlianska DB, Davies C, Chen Y, Olsen SK. Molecular mechanism of a covalent allosteric inhibitor of SUMO E1 activating enzyme. Nat Commun. 2018 12 04; 9(1):5145. PMID: 30514846.
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    7. Young BF, Roth BM, Davies C. 1H, 13C, and 15N resonance assignments of N-acetylmuramyl-L-alanine amidase (AmiC) N-terminal domain (NTD) from Neisseria gonorrhoeae. Biomol NMR Assign. 2019 04; 13(1):63-66. PMID: 30276628.
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    8. Draughn GL, Milton ME, Feldmann EA, Bobay BG, Roth BM, Olson AL, Thompson RJ, Actis LA, Davies C, Cavanagh J. The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism. J Mol Biol. 2018 03 16; 430(6):806-821. PMID: 29438671.
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    9. Hong F, Liu B, Wu BX, Morreall J, Roth B, Davies C, Sun S, Diehl JA, Li Z. CNPY2 is a key initiator of the PERK-CHOP pathway of the unfolded protein response. Nat Struct Mol Biol. 2017 Oct; 24(10):834-839. PMID: 28869608.
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    10. Tomberg J, Fedarovich A, Vincent LR, Jerse AE, Unemo M, Davies C, Nicholas RA. Alanine 501 Mutations in Penicillin-Binding Protein 2 from Neisseria gonorrhoeae: Structure, Mechanism, and Effects on Cephalosporin Resistance and Biological Fitness. Biochemistry. 2017 02 28; 56(8):1140-1150. PMID: 28145684.
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    11. Chen W, Zhang YM, Davies C. Penicillin-Binding Protein 3 Is Essential for Growth of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017 01; 61(1). PMID: 27821444.
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    12. Parasar P, Wilhelm A, Rutigliano HM, Thomas AJ, Teng L, Shi B, Davis WC, Suarez CE, New DD, White KL, Davies CJ. Expression of bovine non-classical major histocompatibility complex class I proteins in mouse P815 and human K562 cells. Res Vet Sci. 2016 Aug; 107:161-170. PMID: 27473990.
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    13. Lenz JD, Stohl EA, Robertson RM, Hackett KT, Fisher K, Xiong K, Lee M, Hesek D, Mobashery S, Seifert HS, Davies C, Dillard JP. Amidase Activity of AmiC Controls Cell Separation and Stem Peptide Release and Is Enhanced by NlpD in Neisseria gonorrhoeae. J Biol Chem. 2016 May 13; 291(20):10916-33. PMID: 26984407.
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    14. Alawieh A, Sabra Z, Bizri AR, Davies C, White R, Zaraket FA. A computational model to monitor and predict trends in bacterial resistance. J Glob Antimicrob Resist. 2015 Sep; 3(3):174-183. PMID: 26640775.
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    15. Fedarovich A, Cook E, Tomberg J, Nicholas RA, Davies C. Structural effect of the Asp345a insertion in penicillin-binding protein 2 from penicillin-resistant strains of Neisseria gonorrhoeae. Biochemistry. 2014 Dec 09; 53(48):7596-603. PMID: 25403720.
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    16. Ranjan R, Dosdall D, Norlund L, Higuchi K, Silvernagel JM, Olsen AL, Davies CJ, MacLeod R, Marrouche NF. Diagnostic imaging and pacemaker implantation in a domestic goat with persistent left cranial vena cava. J Vet Cardiol. 2014 Mar; 16(1):45-50. PMID: 24480717.
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    17. Solomons JT, Johnsen U, Schönheit P, Davies C. 3-Phosphoglycerate is an allosteric activator of pyruvate kinase from the hyperthermophilic archaeon Pyrobaculum aerophilum. Biochemistry. 2013 Aug 27; 52(34):5865-75. PMID: 23879743.
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    18. Dosdall DJ, Ranjan R, Higuchi K, Kholmovski E, Angel N, Li L, Macleod R, Norlund L, Olsen A, Davies CJ, Marrouche NF. Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs. . 2013 Sep 01; 305(5):H725-31. PMID: 23812387.
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    19. Fedarovich A, Djordjevic KA, Swanson SM, Peterson YK, Nicholas RA, Davies C. High-throughput screening for novel inhibitors of Neisseria gonorrhoeae penicillin-binding protein 2. PLoS One. 2012; 7(9):e44918. PMID: 23049763.
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    20. Cunha CW, Gailbreath KL, O'Toole D, Knowles DP, Schneider DA, White SN, Taus NS, Davies CJ, Davis WC, Li H. Ovine herpesvirus 2 infection in American bison: virus and host dynamics in the development of sheep-associated malignant catarrhal fever. Vet Microbiol. 2012 Oct 12; 159(3-4):307-19. PMID: 22592216.
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    21. Fedarovich A, Nicholas RA, Davies C. The role of the ß5-a11 loop in the active-site dynamics of acylated penicillin-binding protein A from Mycobacterium tuberculosis. J Mol Biol. 2012 May 18; 418(5):316-30. PMID: 22365933.
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    22. Nicola G, Tomberg J, Pratt RF, Nicholas RA, Davies C. Crystal structures of covalent complexes of ß-lactam antibiotics with Escherichia coli penicillin-binding protein 5: toward an understanding of antibiotic specificity. Biochemistry. 2010 Sep 21; 49(37):8094-104. PMID: 20726582.
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    23. Fedarovich A, Nicholas RA, Davies C. Unusual conformation of the SxN motif in the crystal structure of penicillin-binding protein A from Mycobacterium tuberculosis. J Mol Biol. 2010 Apr 23; 398(1):54-65. PMID: 20206184.
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    24. Lai TS, Davies C, Greenberg CS. Human tissue transglutaminase is inhibited by pharmacologic and chemical acetylation. Protein Sci. 2010 Feb; 19(2):229-35. PMID: 19998405.
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    25. Demarse NA, Ponnusamy S, Spicer EK, Apohan E, Baatz JE, Ogretmen B, Davies C. Direct binding of glyceraldehyde 3-phosphate dehydrogenase to telomeric DNA protects telomeres against chemotherapy-induced rapid degradation. J Mol Biol. 2009 Dec 11; 394(4):789-803. PMID: 19800890.
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    26. Powell AJ, Tomberg J, Deacon AM, Nicholas RA, Davies C. Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance. J Biol Chem. 2009 Jan 09; 284(2):1202-12. PMID: 18986991.
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    27. Huang Y, Fedarovich A, Tomlinson S, Davies C. Crystal structure of CD59: implications for molecular recognition of the complement proteins C8 and C9 in the membrane-attack complex. Acta Crystallogr D Biol Crystallogr. 2007 Jun; 63(Pt 6):714-21. PMID: 17505110.
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    28. Tsybovsky Y, Donato H, Krupenko NI, Davies C, Krupenko SA. Crystal structures of the carboxyl terminal domain of rat 10-formyltetrahydrofolate dehydrogenase: implications for the catalytic mechanism of aldehyde dehydrogenases. Biochemistry. 2007 Mar 20; 46(11):2917-29. PMID: 17302434.
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    29. Swan MK, Bastia D, Davies C. Crystal structure of pi initiator protein-iteron complex of plasmid R6K: implications for initiation of plasmid DNA replication. Proc Natl Acad Sci U S A. 2006 Dec 05; 103(49):18481-6. PMID: 17124167.
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    30. Fedarovich A, Tomberg J, Nicholas RA, Davies C. Structure of the N-terminal domain of human CEACAM1: binding target of the opacity proteins during invasion of Neisseria meningitidis and N. gonorrhoeae. Acta Crystallogr D Biol Crystallogr. 2006 Sep; 62(Pt 9):971-9. PMID: 16929097.
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    31. Powell AJ, Liu ZJ, Nicholas RA, Davies C. Crystal structures of the lytic transglycosylase MltA from N.gonorrhoeae and E.coli: insights into interdomain movements and substrate binding. J Mol Biol. 2006 May 26; 359(1):122-36. PMID: 16618494.
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    32. Nicola G, Fedarovich A, Nicholas RA, Davies C. A large displacement of the SXN motif of Cys115-modified penicillin-binding protein 5 from Escherichia coli. Biochem J. 2005 Nov 15; 392(Pt 1):55-63. PMID: 16038617.
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    33. Nicola G, Peddi S, Stefanova M, Nicholas RA, Gutheil WG, Davies C. Crystal structure of Escherichia coli penicillin-binding protein 5 bound to a tripeptide boronic acid inhibitor: a role for Ser-110 in deacylation. Biochemistry. 2005 Jun 14; 44(23):8207-17. PMID: 15938610.
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    34. Swan MK, Hansen T, Schönheit P, Davies C. Structural basis for phosphomannose isomerase activity in phosphoglucose isomerase from Pyrobaculum aerophilum: a subtle difference between distantly related enzymes. Biochemistry. 2004 Nov 09; 43(44):14088-95. PMID: 15518558.
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    35. Solomons JT, Zimmerly EM, Burns S, Krishnamurthy N, Swan MK, Krings S, Muirhead H, Chirgwin J, Davies C. The crystal structure of mouse phosphoglucose isomerase at 1.6A resolution and its complex with glucose 6-phosphate reveals the catalytic mechanism of sugar ring opening. J Mol Biol. 2004 Sep 17; 342(3):847-60. PMID: 15342241.
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    36. Swan MK, Hansen T, Schönheit P, Davies C. Crystallization and preliminary X-ray diffraction analysis of phosphoglucose/phosphomannose isomerase from Pyrobaculum aerophilum. Acta Crystallogr D Biol Crystallogr. 2004 Aug; 60(Pt 8):1481-3. PMID: 15272183.
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    37. Swan MK, Hansen T, Schönheit P, Davies C. A novel phosphoglucose isomerase (PGI)/phosphomannose isomerase from the crenarchaeon Pyrobaculum aerophilum is a member of the PGI superfamily: structural evidence at 1.16-A resolution. J Biol Chem. 2004 Sep 17; 279(38):39838-45. PMID: 15252053.
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    38. Chumanevich AA, Krupenko SA, Davies C. The crystal structure of the hydrolase domain of 10-formyltetrahydrofolate dehydrogenase: mechanism of hydrolysis and its interplay with the dehydrogenase domain. J Biol Chem. 2004 Apr 02; 279(14):14355-64. PMID: 14729668.
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    39. Swan MK, Hansen T, Schönheit P, Davies C. Crystallization and preliminary X-ray diffraction analysis of phosphoglucose isomerase from Pyrococcus furiosus. Protein Pept Lett. 2003 Oct; 10(5):517-20. PMID: 14561142.
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    40. Swan MK, Solomons JT, Beeson CC, Hansen T, Schönheit P, Davies C. Structural evidence for a hydride transfer mechanism of catalysis in phosphoglucose isomerase from Pyrococcus furiosus. J Biol Chem. 2003 Nov 21; 278(47):47261-8. PMID: 12970347.
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    41. Davies C, Muirhead H, Chirgwin J. The structure of human phosphoglucose isomerase complexed with a transition-state analogue. Acta Crystallogr D Biol Crystallogr. 2003 Jun; 59(Pt 6):1111-3. PMID: 12777791.
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    42. Davies C, Muirhead H. Structure of native phosphoglucose isomerase from rabbit: conformational changes associated with catalytic function. Acta Crystallogr D Biol Crystallogr. 2003 Mar; 59(Pt 3):453-65. PMID: 12595702.
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    43. Davies C, Muirhead H. Crystal structure of phosphoglucose isomerase from pig muscle and its complex with 5-phosphoarabinonate. Proteins. 2002 Dec 01; 49(4):577-9. PMID: 12402366.
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    44. Chumanevich AA, Davies C, Krupenko SA. Crystallization and preliminary X-ray diffraction analysis of recombinant hydrolase domain of 10-formyltetrahydrofolate dehydrogenase. Acta Crystallogr D Biol Crystallogr. 2002 Oct; 58(Pt 10 Pt 2):1841-2. PMID: 12351832.
      View in: PubMed
    45. Read J, Pearce J, Li X, Muirhead H, Chirgwin J, Davies C. The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia. J Mol Biol. 2001 Jun 01; 309(2):447-63. PMID: 11371164.
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    46. Davies C, White SW, Nicholas RA. Crystal structure of a deacylation-defective mutant of penicillin-binding protein 5 at 2.3-A resolution. J Biol Chem. 2001 Jan 05; 276(1):616-23. PMID: 10967102.
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    47. Davies C, White SW. Electrons and X-rays gang up on the ribosome. Structure. 2000 Mar 15; 8(3):R41-5. PMID: 10745014.
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    48. Davies C, Heath RJ, White SW, Rock CO. The 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from escherichia coli. Structure. 2000 Feb 15; 8(2):185-95. PMID: 10673437.
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    49. Brogdon J, Eckels DD, Davies C, White S, Doyle C. A site for CD4 binding in the beta 1 domain of the MHC class II protein HLA-DR1. J Immunol. 1998 Nov 15; 161(10):5472-80. PMID: 9820523.
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    50. Kugler W, Breme K, Laspe P, Muirhead H, Davies C, Winkler H, Schröter W, Lakomek M. Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency. Hum Genet. 1998 Oct; 103(4):450-4. PMID: 9856489.
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    51. Davies C, Gerstner RB, Draper DE, Ramakrishnan V, White SW. The crystal structure of ribosomal protein S4 reveals a two-domain molecule with an extensive RNA-binding surface: one domain shows structural homology to the ETS DNA-binding motif. EMBO J. 1998 Aug 17; 17(16):4545-58. PMID: 9707415.
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    52. Davies C, Bussiere DE, Golden BL, Porter SJ, Ramakrishnan V, White SW. Ribosomal proteins S5 and L6: high-resolution crystal structures and roles in protein synthesis and antibiotic resistance. J Mol Biol. 1998 Jun 19; 279(4):873-88. PMID: 9642068.
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    53. Clemons WM, Davies C, White SW, Ramakrishnan V. Conformational variability of the N-terminal helix in the structure of ribosomal protein S15. Structure. 1998 Apr 15; 6(4):429-38. PMID: 9562554.
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    54. Finnin MS, Cicero MP, Davies C, Porter SJ, White SW, Kreuzer KN. The activation domain of the MotA transcription factor from bacteriophage T4. EMBO J. 1997 Apr 15; 16(8):1992-2003. PMID: 9155025.
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    55. Davies C, Beauchamp JC, Emery D, Rawas A, Muirhead H. Structure of the Fab fragment from a neutralizing monoclonal antibody directed against an epitope of gp41 from HIV-1. Acta Crystallogr D Biol Crystallogr. 1997 Mar 01; 53(Pt 2):186-94. PMID: 15299953.
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    56. Hoffman DW, Cameron CS, Davies C, White SW, Ramakrishnan V. Ribosomal protein L9: a structure determination by the combined use of X-ray crystallography and NMR spectroscopy. J Mol Biol. 1996 Dec 20; 264(5):1058-71. PMID: 9000630.
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    57. Manna AC, Pai KS, Bussiere DE, Davies C, White SW, Bastia D. Helicase-contrahelicase interaction and the mechanism of termination of DNA replication. Cell. 1996 Nov 29; 87(5):881-91. PMID: 8945515.
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    58. Davies C, Ramakrishnan V, White SW. Structural evidence for specific S8-RNA and S8-protein interactions within the 30S ribosomal subunit: ribosomal protein S8 from Bacillus stearothermophilus at 1.9 A resolution. Structure. 1996 Sep 15; 4(9):1093-104. PMID: 8805594.
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    59. Davies C, White SW, Ramakrishnan V. The crystal structure of ribosomal protein L14 reveals an important organizational component of the translational apparatus. Structure. 1996 Jan 15; 4(1):55-66. PMID: 8805509.
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    60. Ramakrishnan V, Davies C, Gerchman SE, Golden BL, Hoffmann DW, Jaishree TN, Kyila JH, Porter S, White SW. Structures of prokaryotic ribosomal proteins: implications for RNA binding and evolution. Biochem Cell Biol. 1995 Nov-Dec; 73(11-12):979-86. PMID: 8722013.
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    61. Davies C, Gerchman SE, Kycia JH, McGee K, Ramakrishnan V, White SW. Crystallization and preliminary X-ray diffraction studies of bacterial ribosomal protein L14. Acta Crystallogr D Biol Crystallogr. 1994 Sep 01; 50(Pt 5):790-2. PMID: 15299380.
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    62. Hoffman DW, Davies C, Gerchman SE, Kycia JH, Porter SJ, White SW, Ramakrishnan V. Crystal structure of prokaryotic ribosomal protein L9: a bi-lobed RNA-binding protein. EMBO J. 1994 Jan 01; 13(1):205-12. PMID: 8306963.
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    63. Muirhead H, Clayden DA, Cuffe SP, Davies C. Crystallographic studies on the structure and catalytic activity of pyruvate kinase from skeletal muscle. Biochem Soc Trans. 1987 Oct; 15(5):996-9. PMID: 3691955.
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