Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural insights into the vitamin K-dependent γ-carboxylation of osteocalcin.
Journal, issue, pages	Cell Res, Vol. 35, Issue 10, Page 735-749, Year 2025
Publish date	Sep 2, 2025
Authors	Qing Cao / Jianjun Fan / Aaron Ammerman / Samjhana Awasthi / Zongtao Lin / Saimi Mierxiati / Huaping Chen / Jinbin Xu / Benjamin A Garcia / Bin Liu / Weikai Li /
PubMed Abstract	The γ-carboxylation state of osteocalcin determines its essential functions in bone mineralization or systemic metabolism and serves as a prominent biomarker for bone health and vitamin K nutrition. ...The γ-carboxylation state of osteocalcin determines its essential functions in bone mineralization or systemic metabolism and serves as a prominent biomarker for bone health and vitamin K nutrition. This post-translational modification of glutamate residues is catalyzed by the membrane-embedded vitamin K-dependent γ-carboxylase (VKGC), which typically recognizes protein substrates through their tightly bound propeptide that triggers γ-carboxylation. However, the osteocalcin propeptide exhibits negligible affinity for VKGC. To understand the underlying molecular mechanism, we determined the cryo-electron microscopy structures of VKGC with osteocalcin carrying a native propeptide or a high-affinity variant at different carboxylation states. The structures reveal a large chamber in VKGC that maintains uncarboxylated and partially carboxylated osteocalcin in partially unfolded conformations, allowing their glutamate-rich region and C-terminal helices to engage with VKGC at multiple sites. Binding of this mature region together with the low-affinity propeptide effectively stimulates VKGC activity, similar to high-affinity propeptides that differ only in closely fitting interactions. However, the low-affinity propeptide renders osteocalcin prone to undercarboxylation at low vitamin K levels, thereby serving as a discernible biomarker. Overall, our studies reveal the unique interaction of osteocalcin with VKGC and provide a framework for designing therapeutic strategies targeting osteocalcin-related bone and metabolic disorders.
External links	Cell Res / PubMed:40890294 / PubMed Central
Methods	EM (single particle)
Resolution	3.13 - 3.56 Å
Structure data	48519 9mqb EMDB-48519, PDB-9mqb: Vitamin K-dependent gamma-carboxylase with Osteocalcin (mutant) and vitamin K hydroquinone and calcium Method: EM (single particle) / Resolution: 3.37 Å 48520 9mqc EMDB-48520, PDB-9mqc: Vitamin K-dependent gamma-carboxylase with Osteocalcin (mutant) and vitamin K hydroquinone Method: EM (single particle) / Resolution: 3.13 Å 48522 9mqe EMDB-48522, PDB-9mqe: Vitamin K-dependent gamma-carboxylase with Osteocalcin and vitamin K hydroquinone Method: EM (single particle) / Resolution: 3.56 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-6PL: (4S,7R)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSAN-1-AMINIUM 4-OXIDE / phospholipidYM PDB-1avc*: BOVINE ANNEXIN VI (CALCIUM-BOUND)
Source	homo sapiens (human)
Keywords	TRANSFERASE / GGCX / VKGC / Vitamin K / VKCFD / Hemophilia B / Warfarin / Carboxylation / Blood Coagulation / Calcium homeostasis / Osteocalcin / MEMBRANE PROTEIN / calcium