title: With phases: how two wrongs can sometimes make a right.
abstract: In isolation, both weak isomorphous/anomalous difference signals from heavy-atom derivatization and phases from partial molecular-replacement solutions for a subset of the asymmetric unit often fall short of producing interpretable electron-density maps. Phases generated from very partial molecular-replacement models (if generated carefully) can be used to reliably locate heavy-atom sites, even if the signal is not sufficiently strong to allow robust finding of the sites using Patterson interpretation or direct methods. Additional advantages are that using molecular-replacement phases to define the heavy-atom substructure avoids the need for subsequent hand determination and/or origin-choice reconciliation and that the partial model can be used to aid the mask determination during solvent flattening. Two case studies are presented in which it was only by combining experimental and molecular-replacement phasing approaches that the crystal structures could be determined.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, England.
authors.forename: Pietro
authors.initials: P
authors.lastname: Roversi
authors.forename: Steven
authors.initials: S
authors.lastname: Johnson
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lea
mesh_terms: D017242:Complement Factor H / Q000032:analysis / Q000737:chemistry; D018360:Crystallography, X-Ray / Q000379:methods*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H
references.citation: Structure. 2003 Feb;11(2):217-24
references.pmid: 12575941
references.citation: Acta Crystallogr D Biol Crystallogr. 2008 Jan;64(Pt 1):17-24
references.pmid: 18094463
references.citation: J Exp Med. 2007 Oct 1;204(10):2277-83
references.pmid: 17893204
references.citation: J Biol Chem. 2006 Mar 17;281(11):7220-7
references.pmid: 16407174
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1415-20
references.pmid: 11567154
references.citation: Acta Crystallogr D Biol Crystallogr. 2008 Jan;64(Pt 1):108-18
references.pmid: 18094474
references.citation: Methods Mol Biol. 2007;364:215-30
references.pmid: 17172768
references.citation: Protein Eng Des Sel. 2005 Aug;18(8):379-88
references.pmid: 15976010
references.citation: Acta Crystallogr D Biol Crystallogr. 2007 Jan;63(Pt 1):80-93
references.pmid: 17164530
references.citation: Acta Crystallogr D Biol Crystallogr. 2009 Feb;65(Pt 2):101-11
references.pmid: 19171964
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2150-5
references.pmid: 15572768
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):494-506
references.pmid: 11856836
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):108-15
references.pmid: 16369100
references.citation: Curr Opin Struct Biol. 2009 Oct;19(5):566-72
references.pmid: 19700309
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1445-50
references.pmid: 11567158
references.citation: Acta Crystallogr D Biol Crystallogr. 1998 Nov 1;54(Pt 6 Pt 2):1285-94
references.pmid: 10089505
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 Nov;59(Pt 11):1978-86
references.pmid: 14573953
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2210-21
references.pmid: 15572774
references.citation: J Biol Chem. 2007 Jun 29;282(26):18960-8
references.pmid: 17360715
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Jun 1;63(Pt 6):480-3
references.pmid: 17554167
references.citation: Acta Crystallogr D Biol Crystallogr. 2003 Nov;59(Pt 11):1958-65
references.pmid: 14573950
references.citation: Nature. 2009 Apr 16;458(7240):890-3
references.pmid: 19225461
references.citation: J Mol Biol. 1968 Apr 28;33(2):491-7
references.pmid: 5700707