Crystallization to obtain protein-ligand complexes for structure-aided drug design

被引:45
作者
Danley, Dennis E. [1 ]
机构
[1] Pfizer Inc, Pfizer Global Res & Dev, Dept Exploratory Med Sci, Groton, CT 06340 USA
来源
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY | 2006年 / 62卷
关键词
D O I
10.1107/S0907444906012601
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The use of X-ray crystallography to derive three-dimensional structures for structure-aided drug design ( SADD) is a common activity in drug discovery today. In this process, the structures of inhibitors or other ligands of interest complexed with their macromolecular target are solved and the structural information is used iteratively to design new molecules. The ability to form cocrystal complexes between a target protein and a ligand is essential to this process and therefore is of considerable interest to anyone practicing in this field. In the course of obtaining the necessary ligand-protein crystals, even with crystallization conditions well established for a protein of interest, obtaining co-structures with inhibitors either through cocrystallization or soaking is too often not successful. There are numerous potential reasons for this lack of success and this article outlines a number of possible factors that may be involved and discusses considerations that should be taken into account when designing successful experiments to obtain iterative costructures.
引用
收藏
页码:569 / 575
页数:7
相关论文
共 60 条
[41]   Discovery of thrombin inhibitor fragments from chemical microarray screening [J].
Neumann, T ;
Junker, HD ;
Keil, O ;
Burkert, K ;
Ottleben, H ;
Gamer, J ;
Sekul, R ;
Deppe, H ;
Feurer, A ;
Tomandl, D ;
Metz, G .
LETTERS IN DRUG DESIGN & DISCOVERY, 2005, 2 (08) :590-594
[42]   Discovering novel ligands for macromolecules using X-ray crystallographic screening [J].
Nienaber, VL ;
Richardson, PL ;
Klighofer, V ;
Bouska, JJ ;
Giranda, VL ;
Greer, J .
NATURE BIOTECHNOLOGY, 2000, 18 (10) :1105-1108
[43]   A potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2′,5′-dioxospiro[chroman-4,4′-imidazolidine]-2-carboxamide (Fidarestat):: Its absolute configuration and interactions with the aldose reductase by X-ray crystallography [J].
Oka, M ;
Matsumoto, Y ;
Sugiyama, S ;
Tsuruta, N ;
Matsushima, M .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (12) :2479-2483
[44]   Crystal structure of human squalene synthase - A key enzyme in cholesterol biosynthesis [J].
Pandit, J ;
Danley, DE ;
Schulte, GK ;
Mazzalupo, S ;
Pauly, TA ;
Hayward, CM ;
Hamanaka, ES ;
Thompson, JF ;
Harwood, HJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (39) :30610-30617
[45]  
PARGE HE, 1997, RECENT ADV MACROMOLE
[46]   Specificity determinants of human cathepsin S revealed by crystal structures of complexes [J].
Pauly, TA ;
Sulea, T ;
Ammirati, M ;
Sivaraman, J ;
Danley, DE ;
Griffor, MC ;
Kamath, AV ;
Wang, LK ;
Laird, ER ;
Seddon, AP ;
Ménard, R ;
Cygler, M ;
Rath, VL .
BIOCHEMISTRY, 2003, 42 (11) :3203-3213
[47]   PROTEIN ENGINEERING AS A TOOL FOR CRYSTALLOGRAPHY [J].
PRICE, SR ;
NAGAI, K .
CURRENT OPINION IN BIOTECHNOLOGY, 1995, 6 (04) :425-430
[48]   INTERMOLECULAR CROSS LINKING OF PROTEIN IN CRYSTALLINE STATE - CARBOXYPEPTIDASE-A [J].
QUIOCHO, FA ;
RICHARDS, FM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1964, 52 (03) :833-+
[49]   Human liver glycogen phosphorylase inhibitors bind at a new allosteric site [J].
Rath, VL ;
Ammirati, M ;
Danley, DE ;
Ekstrom, JL ;
Gibbs, EM ;
Hynes, TR ;
Mathiowetz, AM ;
McPherson, RK ;
Olson, TV ;
Treadway, JL ;
Hoover, DJ .
CHEMISTRY & BIOLOGY, 2000, 7 (09) :677-682
[50]   Identification and prediction of promiscuous aggregating inhibitors among known drugs [J].
Seidler, J ;
McGovern, SL ;
Doman, TN ;
Shoichet, BK .
JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (21) :4477-4486