{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wu K"],"funding":["National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["10480"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12647623"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["Vitamin K-dependent (VKD) carboxylation, mediated by γ-glutamyl carboxylase (GGCX), is essential for the maturation of VKD proteins involved in critical physiological processes such as blood clotting, vascular calcification and bone metabolism. Here, we present cryo-electron microscopic structures of human GGCX alone and in complex with VKD proteins, vitamin K, and inhibitor anisindione. GGCX specifically recognizes diverse VKD substrates through high-affinity propeptide binding, while substrates like osteocalcin utilize a secondary exosite to enhance interaction. GGCX employs a conserved dipeptide anchoring mechanism that ensures processive carboxylation of glutamate residues. GGCX undergoes allosteric conformational changes that enable coordinated binding of vitamin K and glutamate subst"],"journal":["Nature communications"],"pubmed_title":["Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase."],"pmcid":["PMC12647623"],"funding_grant_id":["31770259","32471344","31570235"],"pubmed_authors":["Wu K","Wu J","Cao M","Lei M","Li S","Lan P","Zhang Y","Yao D","Xing S","Wang X","Shen Y","Wang Z"],"additional_accession":[]},"is_claimable":false,"name":"Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase.","description":"Vitamin K-dependent (VKD) carboxylation, mediated by γ-glutamyl carboxylase (GGCX), is essential for the maturation of VKD proteins involved in critical physiological processes such as blood clotting, vascular calcification and bone metabolism. Here, we present cryo-electron microscopic structures of human GGCX alone and in complex with VKD proteins, vitamin K, and inhibitor anisindione. GGCX specifically recognizes diverse VKD substrates through high-affinity propeptide binding, while substrates like osteocalcin utilize a secondary exosite to enhance interaction. GGCX employs a conserved dipeptide anchoring mechanism that ensures processive carboxylation of glutamate residues. GGCX undergoes allosteric conformational changes that enable coordinated binding of vitamin K and glutamate subst","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T19:54:17.19Z","creation":"2026-05-21T03:11:40.269Z"},"accession":"S-EPMC12647623","cross_references":{"pubmed":["41290650"],"doi":["10.1038/s41467-025-65488-3"]}}