Suzuki M
MRC Laboratory of Molecular Biology, Cambridge, UK.
Structure. 1994 Apr 15;2(4):317-26. doi: 10.1016/s0969-2126(00)00033-2.
Understanding the general mechanisms of sequence specific DNA recognition by proteins is a major challenge in structural biology. The existence of a 'DNA recognition code' for proteins, by which certain amino acid residues on a protein surface confer specificity for certain DNA bases, has been the subject of much discussion. However, no simple code has yet been established.
The principles of DNA recognition can be described at two levels. The 'chemical' rules describe the partnerships between amino acid side chains and DNA bases making favourable interactions in the major groove of DNA. Here I analyze the occurrence of nucleotide-amino acid contacts in previously determined crystal structures of DNA-protein complexes and find that simple rules pertain. I also describe 'stereochemical' rules for the probe helix type of DNA-binding motif found in certain transcription factors including leucine zipper and homeodomain proteins. These are a consequence of the binding geometry, and specify the amino acid and base positions used for the contacts, and the sizes of residues in the contact interface.
The chemical rules can be generalized for any DNA-binding motif, while the stereochemical rules are specific to a particular DNA-binding motif. The recognition code for a particular binding motif can be described by combining the two sets of rules.
了解蛋白质对特定序列DNA的识别的一般机制是结构生物学中的一项重大挑战。蛋白质存在“DNA识别密码”，即蛋白质表面的某些氨基酸残基赋予对某些DNA碱基的特异性，这一话题已被广泛讨论。然而，尚未建立简单的密码。
DNA识别的原理可在两个层面描述。“化学”规则描述了在DNA大沟中形成有利相互作用的氨基酸侧链与DNA碱基之间的配对关系。在此，我分析了先前确定的DNA-蛋白质复合物晶体结构中核苷酸-氨基酸接触的情况，发现存在简单规则。我还描述了在某些转录因子（包括亮氨酸拉链和同源结构域蛋白）中发现的DNA结合基序的探针螺旋类型的“立体化学”规则。这些是结合几何结构的结果，并指定了用于接触的氨基酸和碱基位置，以及接触界面中残基的大小。
化学规则可推广到任何DNA结合基序，而立体化学规则特定于特定的DNA结合基序。特定结合基序的识别密码可通过结合这两组规则来描述。
