General Information

Database accession: MF2100001

Name: Human parathyroid hormone

PDB ID: 1et1 PDB

Experimental method: X-ray (0.90 Å)

Assembly: homodimer

Source organism: Homo sapiens

Primer publication of the structure:

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.
(2000) J. Biol. Chem. 275: 27238-44

PMID: 10837469 PubMed

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.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Interacting selectively and non-covalently with a sequence of DNA that is in a distal enhancer region for RNA polymerase II (RNAP II) in order to modulate transcription by RNAP II. GeneOntology

peptide hormone receptor binding Interacting selectively and non-covalently with a receptor for peptide hormones. GeneOntology

hormone activity The action characteristic of a hormone, any substance formed in very small amounts in one specialized organ or group of cells and carried (sometimes in the bloodstream) to another organ or group of cells in the same organism, upon which it has a specific regulatory action. The term was originally applied to agents with a stimulatory physiological action in vertebrate animals (as opposed to a chalone, which has a depressant action). Usage is now extended to regulatory compounds in lower animals and plants, and to synthetic substances having comparable effects; all bind receptors and trigger some biological process. GeneOntology

type 1 parathyroid hormone receptor binding Interacting selectively and non-covalently with a type 1 parathyroid hormone receptor. GeneOntology

Biological process:

negative regulation of transcription from RNA polymerase II promoter Any process that stops, prevents, or reduces the frequency, rate or extent of transcription from an RNA polymerase II promoter. GeneOntology

response to cadmium ion Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cadmium (Cd) ion stimulus. GeneOntology

adenylate cyclase-activating G-protein coupled receptor signaling pathway The series of molecular signals generated as a consequence of a G-protein coupled receptor binding to its physiological ligand, where the pathway proceeds through activation of adenylyl cyclase activity and a subsequent increase in the concentration of cyclic AMP (cAMP). GeneOntology

positive regulation of osteoclast proliferation Any process that increases the rate, frequency, or extent of the multiplication or reproduction of osteoclasts, resulting in the expansion of an osteoclast cell population. GeneOntology

hormone-mediated apoptotic signaling pathway A series of molecular signals mediated by the detection of a hormone, and which triggers the apoptotic signaling pathway in a cell. The pathway starts with reception of a hormone signal, and ends when the execution phase of apoptosis is triggered. GeneOntology

positive regulation of cell proliferation in bone marrow A process that activates or increases the frequency, rate or extent of cell proliferation in the bone marrow. GeneOntology

homeostasis of number of cells within a tissue Any biological process involved in the maintenance of the steady-state number of cells within a population of cells in a tissue. GeneOntology

positive regulation of glycogen biosynthetic process Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of glycogen. GeneOntology

positive regulation of glucose import Any process that activates or increases the frequency, rate or extent of the import of the hexose monosaccharide glucose into a cell or organelle. GeneOntology

response to lead ion Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lead ion stimulus. GeneOntology

positive regulation of transcription from RNA polymerase II promoter Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. GeneOntology

positive regulation of bone mineralization Any process that activates or increases the frequency, rate or extent of bone mineralization. GeneOntology

cAMP metabolic process The chemical reactions and pathways involving the nucleotide cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate). GeneOntology

Rho protein signal transduction A series of molecular signals within the cell that are mediated by a member of the Rho family of proteins switching to a GTP-bound active state. GeneOntology

response to parathyroid hormone Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a parathyroid hormone stimulus. GeneOntology

negative regulation of apoptotic process in bone marrow Any process that stops, prevents, or reduces the frequency, rate or extent of the occurrence or rate of cell death by apoptotic process in the bone marrow. GeneOntology

response to ethanol Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ethanol stimulus. GeneOntology

cellular calcium ion homeostasis Any process involved in the maintenance of an internal steady state of calcium ions at the level of a cell. GeneOntology

cellular macromolecule biosynthetic process The chemical reactions and pathways resulting in the formation of a macromolecule, any molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass, carried out by individual cells. GeneOntology

positive regulation of signal transduction Any process that activates or increases the frequency, rate or extent of signal transduction. GeneOntology

response to drug Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a drug stimulus. A drug is a substance used in the diagnosis, treatment or prevention of a disease. GeneOntology

skeletal system development The process whose specific outcome is the progression of the skeleton over time, from its formation to the mature structure. The skeleton is the bony framework of the body in vertebrates (endoskeleton) or the hard outer envelope of insects (exoskeleton or dermoskeleton). GeneOntology

cell-cell signaling Any process that mediates the transfer of information from one cell to another. This process includes signal transduction in the receiving cell and, where applicable, release of a ligand and any processes that actively facilitate its transport and presentation to the receiving cell. Examples include signaling via soluble ligands, via cell adhesion molecules and via gap junctions. GeneOntology

response to fibroblast growth factor Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a fibroblast growth factor stimulus. GeneOntology

response to vitamin D Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vitamin D stimulus. GeneOntology

positive regulation of cAMP biosynthetic process Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of the nucleotide cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate). GeneOntology

bone resorption The process in which specialized cells known as osteoclasts degrade the organic and inorganic portions of bone, and endocytose and transport the degradation products. GeneOntology

Cellular component:

intracellular The living contents of a cell; the matter contained within (but not including) the plasma membrane, usually taken to exclude large vacuoles and masses of secretory or ingested material. In eukaryotes it includes the nucleus and cytoplasm. GeneOntology

extracellular space That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: A, B

Notes: No modifications of the original PDB file. Chain identifiers are identical with the PDB's identifiers.

Number of unique protein segments: 1

Chain A

Name: Parathyroid hormone

Source organism: Homo sapiens

Length: 34 residues

Sequence:Sequence according to PDB SEQRESSVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF

UniProtKB AC: P01270 (positions: 32-65) UniProt Coverage: 29.6%

UniRef90 AC: UniRef90_P01270 (positions: 32-65) UniRef90

Chain B

Name: Parathyroid hormone

Source organism: Homo sapiens

Length: 34 residues

Sequence:Sequence according to PDB SEQRESSVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF

UniProtKB AC: P01270 (positions: 32-65) UniProt Coverage: 29.6%

UniRef90 AC: UniRef90_P01270 (positions: 32-65) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Chain A:

The 32-65 region described in DisProt entry DP00637 covers 100% of the sequence present in the structure.

Chain B:

The 32-65 region described in DisProt entry DP00637 covers 100% of the sequence present in the structure.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

No related structure was found in the Protein Data Bank.

The molecule viewer shows the original PDB stucture.

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