3n7r

Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals the site of drug antagonism

Method: X-RAY DIFFRACTION Dmax: 78.0 Å Quality: GOOD

1. 蛋白身份与相关结构 Protein Identity & Related Structures

Calcitonin gene-related peptide type 1 receptor

Homo sapiens

UniProt Q16602

当前结构中的状态

Assembly 聚集状态 构建体 突变与修饰 配体、离子与共同组分 实验方法与环境 结构质量
1 蛋白异源复合物 异源复合物 蛋白 × 2 PDB 声明:dimeric(2) 与蛋白拷贝数一致 链 A; UniProt 23–133 片段:UNP residues 23-133 Receptor activity-modifying protein 1 × 1 (O60894) 3N6 N-{(1S)-5-amino-1-[(4-pyridin-4-ylpiperazin-1-yl)carbonyl]pentyl}-3,5-dibromo-Nalpha-{[4-(2-oxo-1,4-dihydroquinazolin-3 (2H)-yl)piperidin-1-yl]carbonyl}-D-tyrosinamide × 1 X-RAY DIFFRACTION X-ray结晶条件:VAPOR DIFFUSION, HANGING DROP;pH 6.5;298 K;CLR/RAMP1 complex was mixed with Olcegepant prior to crystallization in a 1:4 (protein : compound) molar ratio. Crystals were obtained by mixing 0.6uL protein with 0.3uL reservoir solution containing 1-1.3M ammonium sulfate, 6-8% dioxane, 60-80mM MES pH 6.5, plus 0.4 M potassium thiocyanate. Telcagepant was soaked into the ligand binding site. The crystal was transferred to 2.1M NaMalonate (pH 7.0) prior to freezing in liquid nitrogen., VAPOR DIFFUSION, HANGING DROP, temperature 298K 分辨率 2.90 Å R-free 0.267
2 蛋白异源复合物 异源复合物 蛋白 × 2 PDB 声明:dimeric(2) 与蛋白拷贝数一致 链 B; UniProt 23–133 片段:UNP residues 23-133 Receptor activity-modifying protein 1 × 1 (O60894) N7R N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide × 1 X-RAY DIFFRACTION X-ray结晶条件:VAPOR DIFFUSION, HANGING DROP;pH 6.5;298 K;CLR/RAMP1 complex was mixed with Olcegepant prior to crystallization in a 1:4 (protein : compound) molar ratio. Crystals were obtained by mixing 0.6uL protein with 0.3uL reservoir solution containing 1-1.3M ammonium sulfate, 6-8% dioxane, 60-80mM MES pH 6.5, plus 0.4 M potassium thiocyanate. Telcagepant was soaked into the ligand binding site. The crystal was transferred to 2.1M NaMalonate (pH 7.0) prior to freezing in liquid nitrogen., VAPOR DIFFUSION, HANGING DROP, temperature 298K 分辨率 2.90 Å R-free 0.267

数据库中的同蛋白其他状态

以下每一行都是同一 UniProt 蛋白在另一个 PDB 条目中的 biological assembly, “相对当前条目”直接指出证据层面的不同;没有差异标签表示当前已读取字段一致。

共 24 个其他 PDB 条目、36 个 assembly。 打开独立比较页并筛选聚集状态

查看构建体与数据证据
UniProt名称 CALRL_HUMAN
Isoform
PDB实体 1
链与序列区间 作者链 A; PDB构建体 5–115; UniProt 23–133 作者链 B; PDB构建体 5–115; UniProt 23–133

Receptor activity-modifying protein 1

Homo sapiens

UniProt O60894

当前结构中的状态

Assembly 聚集状态 构建体 突变与修饰 配体、离子与共同组分 实验方法与环境 结构质量
1 蛋白异源复合物 异源复合物 蛋白 × 2 PDB 声明:dimeric(2) 与蛋白拷贝数一致 链 D; UniProt 26–117 片段:Extra-cellular domain residues 26-117 Calcitonin gene-related peptide type 1 receptor × 1 (Q16602) 3N6 N-{(1S)-5-amino-1-[(4-pyridin-4-ylpiperazin-1-yl)carbonyl]pentyl}-3,5-dibromo-Nalpha-{[4-(2-oxo-1,4-dihydroquinazolin-3 (2H)-yl)piperidin-1-yl]carbonyl}-D-tyrosinamide × 1 X-RAY DIFFRACTION X-ray结晶条件:VAPOR DIFFUSION, HANGING DROP;pH 6.5;298 K;CLR/RAMP1 complex was mixed with Olcegepant prior to crystallization in a 1:4 (protein : compound) molar ratio. Crystals were obtained by mixing 0.6uL protein with 0.3uL reservoir solution containing 1-1.3M ammonium sulfate, 6-8% dioxane, 60-80mM MES pH 6.5, plus 0.4 M potassium thiocyanate. Telcagepant was soaked into the ligand binding site. The crystal was transferred to 2.1M NaMalonate (pH 7.0) prior to freezing in liquid nitrogen., VAPOR DIFFUSION, HANGING DROP, temperature 298K 分辨率 2.90 Å R-free 0.267
2 蛋白异源复合物 异源复合物 蛋白 × 2 PDB 声明:dimeric(2) 与蛋白拷贝数一致 链 C; UniProt 26–117 片段:Extra-cellular domain residues 26-117 Calcitonin gene-related peptide type 1 receptor × 1 (Q16602) N7R N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide × 1 X-RAY DIFFRACTION X-ray结晶条件:VAPOR DIFFUSION, HANGING DROP;pH 6.5;298 K;CLR/RAMP1 complex was mixed with Olcegepant prior to crystallization in a 1:4 (protein : compound) molar ratio. Crystals were obtained by mixing 0.6uL protein with 0.3uL reservoir solution containing 1-1.3M ammonium sulfate, 6-8% dioxane, 60-80mM MES pH 6.5, plus 0.4 M potassium thiocyanate. Telcagepant was soaked into the ligand binding site. The crystal was transferred to 2.1M NaMalonate (pH 7.0) prior to freezing in liquid nitrogen., VAPOR DIFFUSION, HANGING DROP, temperature 298K 分辨率 2.90 Å R-free 0.267

数据库中的同蛋白其他状态

以下每一行都是同一 UniProt 蛋白在另一个 PDB 条目中的 biological assembly, “相对当前条目”直接指出证据层面的不同;没有差异标签表示当前已读取字段一致。

共 25 个其他 PDB 条目、38 个 assembly。 打开独立比较页并筛选聚集状态

查看构建体与数据证据
UniProt名称 RAMP1_HUMAN
Isoform
PDB实体 2
链与序列区间 作者链 C; PDB构建体 5–96; UniProt 26–117 作者链 D; PDB构建体 5–96; UniProt 26–117

页面优先展示蛋白身份、当前 assembly、共同组分、聚集状态和跨 PDB 结构链接。 链映射与序列区间收在“数据证据”中;数据库内部编号、导入时间和 assembly 操作表达式仅用于维护,因此不在读者页面展示。

SAXS 散射曲线 SAXS Profile

SAXS profile for 3n7r

P(r) 距离分布 P(r) Distribution

P(r) distribution for 3n7r
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2. 结构基本信息 2. Structure Basics

条目编号 entry_id3n7r
沉积日期 deposition_date2010-05-27
结构标题 titleCrystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals the site of drug antagonism
关键词 keywordsGPCR, class B GPCR, antagonist, olcegepant, telcagepant, migraine, MEMBRANE PROTEIN; MEMBRANE PROTEIN
实验方法 methodX-RAY DIFFRACTION

3. SAXS 参数 (CRYSOL 理论计算) 3. SAXS Parameters (CRYSOL)

回转半径 Rg (Guinier) rg_guinier24.05
回转半径 Rg (电子) rg_electron23.24
零角强度 I(0) i030359800.00
分子量 molecular_weight39787.0 kDa
排除体积 excluded_volume48387 ų
包络体积 envelope_volume59359 ų
水化壳体积 shell_volume21934 ų
包络直径 envelope_diameter79.0
壳层 Rg shell_rg29.66
包络 Rg envelope_rg23.39
形状 Rg shape_rg23.22
总 Rg total_rg24.04
总原子数 total_atoms2786
残基数 n_residues345
球谐函数阶数 n_harmonics20
q 范围 q_range— – 0.5000 −1
数据点数 n_points101
壳层类型 shell_typedirectional
溶剂电子密度 solvent_density0.3340 e/ų
壳层衬度 contrast_shell0.0300 e/ų
CRYSOL 版本 crysol_version4.1.3

4. P(r) 距离分布 (GNOM 反演) 4. P(r) Analysis (GNOM)

最大尺寸 Dmax dmax78.0
Rg (实空间) rg_real24.07
Rg 误差 (实空间) rg_real_error0.56
I(0) (实空间) i0_real3.0360e+07
I(0) 误差 (实空间) i0_real_error3.9250e+05
Rg (倒空间) rg_reciprocal24.07
I(0) (倒空间) i0_reciprocal30360000.0000
解质量估计 total_estimate0.8995
解质量评级 solution_quality GOOD a GOOD solution
P(r) 峰数 n_peaks2
主峰位置 r_peak_primary25.6
偏度 Skewness skewness0.329
峰度 Kurtosis kurtosis-0.496
角度范围 angular_range— – 0.3300 −1
当前正则化参数 α current_alpha0.0000
最高正则化参数 α highest_alpha4087000.0000
实空间数据点数 n_real_points65
GNOM 版本 gnom_version4.1.3
质量判据 quality_criteria AN1: 0.000; Oscil: 0.915; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.962; Smooth: 0.982

5. 晶体学与实验 5. Crystallography & Experiment

6. 实体与聚合物信息 Entities & Polymers (5)

7. 折叠分类 (SCOP + CATH) 4 domains

CATH v4.4 (4 domains)

结构域编号 domain_id3n7rA00
类 Class class4 — Few Secondary Structures
架构 Architecture architecture10 — Irregular
拓扑 Topology topology1240 — Hormone receptor fold
同源超家族 H-superfamily homologous superfamily10 — GPCR, family 2, extracellular hormone receptor domain
结构域编号 domain_id3n7rB00
类 Class class4 — Few Secondary Structures
架构 Architecture architecture10 — Irregular
拓扑 Topology topology1240 — Hormone receptor fold
同源超家族 H-superfamily homologous superfamily10 — GPCR, family 2, extracellular hormone receptor domain
结构域编号 domain_id3n7rC00
类 Class class1 — Mainly Alpha
架构 Architecture architecture10 — Orthogonal Bundle
拓扑 Topology topology150 — DNA polymerase; domain 1
同源超家族 H-superfamily homologous superfamily510 — Receptor activity modifying family
结构域编号 domain_id3n7rD00
类 Class class1 — Mainly Alpha
架构 Architecture architecture10 — Orthogonal Bundle
拓扑 Topology topology150 — DNA polymerase; domain 1
同源超家族 H-superfamily homologous superfamily510 — Receptor activity modifying family

8. 引用文献 (1)

9. 文件与曲线 (10)