Crystal structure of human parathyroid hormone 1-34 at 0.9-A resolution.

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Jin L, Briggs SL, Chandrasekhar S, Chirgadze NY, Clawson DK, Schevitz RW, Smiley DL, Tashjian AH, Zhang F

Crystal structure of human parathyroid hormone 1-34 at 0.9-A resolution.

J Biol Chem. 2000 Sep 1;275(35):27238-44.

PubMed ID

10837469 [ View in PubMed

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Abstract

The N-terminal fragment 1-34 of parathyroid hormone (PTH), administered intermittently, results in increased bone formation in patients with osteoporosis. PTH and a related molecule, parathyroid hormone-related peptide (PTHrP), act on cells via a common PTH/PTHrP receptor. To define more precisely the ligand-receptor interactions, we have crystallized human PTH (hPTH)-(1-34) and determined the structure to 0.9-A resolution. hPTH-(1-34) crystallizes as a slightly bent, long helical dimer. Analysis reveals that the extended helical conformation of hPTH-(1-34) is the likely bioactive conformation. We have developed molecular models for the interaction of hPTH-(1-34) and hPTHrP-(1-34) with the PTH/PTHrP receptor. A receptor binding pocket for the N terminus of hPTH-(1-34) and a hydrophobic interface with the receptor for the C terminus of hPTH-(1-34) are proposed.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Parathyroid hormone	Parathyroid hormone 2 receptor	Protein	Humans	Yes	Activator	Details
Parathyroid hormone	Parathyroid hormone/parathyroid hormone-related peptide receptor	Protein	Humans	Unknown	Activator	Details

Polypeptides

Name	UniProt ID
Parathyroid hormone	P01270	Details