SASDEN5: AMP/fumarate-bound neanderthal adenylosuccinate lyase (ADSL)

基本情報

• 登録情報: データベース: SASBDB / ID: SASDEN5

試料

AMP/fumarate-bound neanderthal adenylosuccinate lyase (ADSL)

• Adenylosuccinate Lyase (protein), ADSL, Homo sapiens neanderthalensis

• 生物種: Homo sapiens neanderthalensis (ヒト)
• 引用: ジャーナル: Sci Rep / 年: 2018; タイトル: Molecular comparison of Neanderthal and Modern Human adenylosuccinate lyase.; 著者: Bart Van Laer / Ulrike Kapp / Montserrat Soler-Lopez / Kaja Moczulska / Svante Pääbo / Gordon Leonard / Christoph Mueller-Dieckmann / ; 要旨: The availability of genomic data from extinct homini such as Neanderthals has caused a revolution in palaeontology allowing the identification of modern human-specific protein substitutions. Currently, little is known as to how these substitutions alter the proteins on a molecular level. Here, we investigate adenylosuccinate lyase, a conserved enzyme involved in purine metabolism for which several substitutions in the modern human protein (hADSL) have been described to affect intelligence and behaviour. During evolution, modern humans acquired a specific substitution (Ala429Val) in ADSL distinguishing it from the ancestral variant present in Neanderthals (nADSL). We show here that despite this conservative substitution being solvent exposed and located distant from the active site, there is a difference in thermal stability, but not enzymology or ligand binding between nADSL and hADSL. Substitutions near residue 429 which do not profoundly affect enzymology were previously reported to cause neurological symptoms in humans. This study also reveals that ADSL undergoes conformational changes during catalysis which, together with the crystal structure of a hitherto undetermined product bound conformation, explains the molecular origin of disease for several modern human ADSL mutants.

登録者

• Bart Van Laer (ESRF, European Synchrotron Radiation Facility, Grenoble, France)

モデル

• モデル #2431: ; タイプ: atomic / カイ2乗値: 3.171; Omokage検索でこの集合体の類似形状データを探す (詳細)

試料

• 試料: 名称: AMP/fumarate-bound neanderthal adenylosuccinate lyase (ADSL); 試料濃度: 5 mg/ml
• バッファ: 名称: 10 mM HEPES, 100 mM NaCl, 1 mM DTT, 1mM AMP, 1mM Fumarate; pH: 7.5

要素 #1311

名称: ADSL / タイプ: protein / 記述: Adenylosuccinate Lyase / 分子量: 55.142 / 分子数: 4 / 由来: Homo sapiens neanderthalensis
配列:

GSHMAAGGDH GSPDSYRSPL ASRYASPEMC FVFSDRYKFR TWRQLWLWLA EAEQTLGLPI TDEQIQEMKS NLENIDFKMA AEEEKRLRHD VMAHVHTFGH CCPKAAGIIH LGATSCYVGD NTDLIILRNA LDLLLPKLAR VISRLADFAK ERASLPTLGF THFQPAQLTT VGKRCCLWIQ DLCMDLQNLK RVRDDLRFRG VKGTTGTQAS FLQLFEGDDH KVEQLDKMVT EKAGFKRAFI ITGQTYTRKV DIEVLSVLAS LGASVHKICT DIRLLANLKE MEEPFEKQQI GSSAMPYKRN PMRSERCCSL ARHLMTLVMD PLQTASVQWF ERTLDDSANR RICLAEAFLT ADTILNTLQN ISEGLVVYPK VIERRIRQEL PFMATENIIM AMVKAGGSRQ DCHEKIRVLS QQAASVVKQE GGDNDLIERI QADAYFSPIH SQLDHLLDPS SFTGRASQQV QRFLEEEVYP LLKPYESVMK VKAELCL

実験情報

• ビーム: 設備名称: ESRF BM29 / 地域: Grenoble / 国: France / 線源: X-ray synchrotron / 波長: 0.099 Å / スペクトロメータ・検出器間距離: 2.864 mm
• 検出器: 名称: Pilatus 1M / タイプ: Dectris / Pixsize x: 172 mm

スキャン

タイトル: AMP/fumarate-bound neanderthal adenylosuccinate lyase (ADSL)
測定日: 2016年7月24日 / 保管温度: 20 °C / セル温度: 20 °C / 照射時間: 1 sec. / フレーム数: 10 / 単位: 1/nm /

	Min	Max
Q	0.0467	3.8035

結果

カーブのタイプ: single_conc /

	実験値	Porod
分子量	168 kDa	161 kDa
体積	-	258 nm3

	Guinier	Guinier error
前方散乱 I0	152.55	0.05
慣性半径, Rg	3.65 nm	0.01

	Min	Max
Guinier point	6	66