登録情報 データベース : PDB / ID : 7mhz 構造の表示 ダウンロードとリンクタイトル Human Hedgehog acyltransferase (HHAT) in complex with a palmitoylated Hedgehog peptide product and a Fab antibody fragment 要素3H02 Fab heavy chain 3H02 Fab light chain Protein-cysteine N-palmitoyltransferase HHAT Sonic hedgehog protein N-product peptide 詳細キーワード TRANSFERASE/IMMUNE SYSTEM / MBOAT / GOAT / porcupine / acyl transferase / membrane protein / membrane enzyme / ER / palmitoyl-CoA / TRANSFERASE-IMMUNE SYSTEM complex機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
N-terminal peptidyl-L-cysteine N-palmitoylation / Formation of lateral plate mesoderm / positive regulation of skeletal muscle cell proliferation / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation ... N-terminal peptidyl-L-cysteine N-palmitoylation / Formation of lateral plate mesoderm / positive regulation of skeletal muscle cell proliferation / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation / positive regulation of ureter smooth muscle cell differentiation / negative regulation of kidney smooth muscle cell differentiation / positive regulation of kidney smooth muscle cell differentiation / morphogen activity / regulation of odontogenesis / positive regulation of mesenchymal cell proliferation involved in ureter development / polarity specification of anterior/posterior axis / trunk neural crest cell migration / hindgut morphogenesis / O-acyltransferase activity / striated muscle tissue development / negative regulation of alpha-beta T cell differentiation / regulation of glial cell proliferation / regulation of prostatic bud formation / metanephric mesenchymal cell proliferation involved in metanephros development / formation of anatomical boundary / lung epithelium development / positive regulation of striated muscle cell differentiation / ventral midline development / trachea morphogenesis / cholesterol-protein transferase activity / bud outgrowth involved in lung branching / HHAT G278V doesn't palmitoylate Hh-Np / telencephalon regionalization / epithelial-mesenchymal cell signaling / laminin-1 binding / Ligand-receptor interactions / salivary gland cavitation / negative regulation of cholesterol efflux / determination of left/right asymmetry in lateral mesoderm / spinal cord dorsal/ventral patterning / negative regulation of mesenchymal cell apoptotic process / cell development / positive regulation of cerebellar granule cell precursor proliferation / negative regulation of T cell differentiation in thymus / palmitoyltransferase activity / spinal cord motor neuron differentiation / positive regulation of T cell differentiation in thymus / intermediate filament organization / cerebellar granule cell precursor proliferation / mesenchymal cell apoptotic process / embryonic skeletal system development / limb bud formation / lung lobe morphogenesis / prostate gland development / Activation of SMO / skeletal muscle fiber differentiation / establishment of epithelial cell polarity / thalamus development / embryonic digestive tract morphogenesis / embryonic foregut morphogenesis / somite development / patched binding / epithelial cell proliferation involved in salivary gland morphogenesis / hindbrain development / positive regulation of skeletal muscle tissue development / animal organ formation / ectoderm development / neuron fate commitment / stem cell development / dorsal/ventral neural tube patterning / negative regulation of dopaminergic neuron differentiation / mesenchymal cell proliferation involved in lung development / negative thymic T cell selection / skeletal muscle cell proliferation / lymphoid progenitor cell differentiation / positive regulation of immature T cell proliferation in thymus / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / smooth muscle tissue development / regulation of stem cell proliferation / oligodendrocyte development / male genitalia development / artery development / positive regulation of astrocyte differentiation / pattern specification process / self proteolysis / epithelial cell proliferation involved in prostate gland development / positive regulation of epithelial cell proliferation involved in prostate gland development / embryonic pattern specification / branching involved in salivary gland morphogenesis / Release of Hh-Np from the secreting cell / Formation of axial mesoderm / lung-associated mesenchyme development / dopaminergic neuron differentiation / regulation of proteolysis / metanephros development / positive thymic T cell selection / intein-mediated protein splicing / glycosaminoglycan binding 類似検索 - 分子機能 Hedgehog, N-terminal signalling domain / Hedgehog protein / Hedgehog protein, Hint domain / Hint module / Hedgehog amino-terminal signalling domain / Membrane bound O-acyl transferase, MBOAT / MBOAT, membrane-bound O-acyltransferase family / Hedgehog signalling/DD-peptidase zinc-binding domain superfamily / Hint domain C-terminal / Hint (Hedgehog/Intein) domain C-terminal region ... Hedgehog, N-terminal signalling domain / Hedgehog protein / Hedgehog protein, Hint domain / Hint module / Hedgehog amino-terminal signalling domain / Membrane bound O-acyl transferase, MBOAT / MBOAT, membrane-bound O-acyltransferase family / Hedgehog signalling/DD-peptidase zinc-binding domain superfamily / Hint domain C-terminal / Hint (Hedgehog/Intein) domain C-terminal region / Intein N-terminal splicing region / Intein N-terminal splicing motif profile. / Hint domain N-terminal / Hint (Hedgehog/Intein) domain N-terminal region / Hint domain superfamily 類似検索 - ドメイン・相同性 PROTOPORPHYRIN IX CONTAINING FE / Palmitoyl-CoA / PALMITIC ACID / Sonic hedgehog protein / Protein-cysteine N-palmitoyltransferase HHAT 類似検索 - 構成要素生物種 Homo sapiens (ヒト)Mus musculus (ハツカネズミ)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.2 Å 詳細データ登録者 Long, S.B. / Jiang, Y. 資金援助 米国, 2件 詳細 詳細を隠す組織 認可番号 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R35GM131921 米国 National Institutes of Health/National Cancer Institute (NIH/NCI) P30CA008748 米国
引用ジャーナル : Science / 年 : 2021タイトル : Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT.著者 : Yiyang Jiang / Thomas L Benz / Stephen B Long / 要旨 : Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino- ... Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). We present cryo-electron microscopy structures of human HHAT in complex with its palmitoyl-coenzyme A substrate and of a product complex with a palmitoylated Hedgehog peptide at resolutions of 2.7 and 3.2 angstroms, respectively. The structures reveal how HHAT overcomes the challenges of bringing together substrates that have different physiochemical properties from opposite sides of the endoplasmic reticulum membrane within a membrane-embedded active site for catalysis. These principles are relevant to related enzymes that catalyze the acylation of Wnt and of the appetite-stimulating hormone ghrelin. The structural and mechanistic insights may advance the development of inhibitors for cancer. 履歴 登録 2021年4月16日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2021年6月16日 Provider : repository / タイプ : Initial release改定 1.1 2021年7月14日 Group : Database references / カテゴリ : citationItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title 改定 2.0 2021年8月25日 Group : Advisory / Atomic model ... Advisory / Atomic model / Data collection / Database references カテゴリ : atom_site / database_2 ... atom_site / database_2 / database_PDB_caveat / pdbx_unobs_or_zero_occ_atoms / pdbx_validate_chiral Item : _atom_site.Cartn_x / _atom_site.Cartn_y ... _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_atom_id / _atom_site.label_atom_id / _atom_site.type_symbol / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_unobs_or_zero_occ_atoms.auth_atom_id / _pdbx_unobs_or_zero_occ_atoms.label_atom_id
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