View source for 1uz9

==CRYSTALLOGRAPHIC AND SOLUTION STUDIES OF N-LITHOCHOLYL INSULIN: A NEW GENERATION OF PROLONGED-ACTING INSULINS.==
<StructureSection load='1uz9' size='340' side='right' caption='[[1uz9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1uz9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UZ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UZ9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CRS:M-CRESOL'>CRS</scene>, <scene name='pdbligand=UZ9:(2S)-2-AMINO-6-({(4R)-4-[(10R,13S)-10,13-DIMETHYL-3-OXOHEXADECAHYDRO-1H-CYCLOPENTA[A]PHENANTHREN-17-YL]PENTANOYL}AMINO)HEXANOIC+ACID'>UZ9</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a7f|1a7f]], [[1ai0|1ai0]], [[1aiy|1aiy]], [[1b9e|1b9e]], [[1ben|1ben]], [[1efe|1efe]], [[1ev3|1ev3]], [[1ev6|1ev6]], [[1evr|1evr]], [[1fu2|1fu2]], [[1fub|1fub]], [[1g7a|1g7a]], [[1g7b|1g7b]], [[1guj|1guj]], [[1hiq|1hiq]], [[1his|1his]], [[1hit|1hit]], [[1hls|1hls]], [[1htv|1htv]], [[1hui|1hui]], [[1iog|1iog]], [[1ioh|1ioh]], [[1j73|1j73]], [[1jca|1jca]], [[1jco|1jco]], [[1k3m|1k3m]], [[1kmf|1kmf]], [[1lkq|1lkq]], [[1lnp|1lnp]], [[1lph|1lph]], [[1mhi|1mhi]], [[1mhj|1mhj]], [[1mso|1mso]], [[1os3|1os3]], [[1os4|1os4]], [[1q4v|1q4v]], [[1qiy|1qiy]], [[1qiz|1qiz]], [[1qj0|1qj0]], [[1sjt|1sjt]], [[1sju|1sju]], [[1trz|1trz]], [[1tyl|1tyl]], [[1tym|1tym]], [[1vkt|1vkt]], [[1xda|1xda]], [[1xgl|1xgl]], [[1zeg|1zeg]], [[1zeh|1zeh]], [[1znj|1znj]], [[2aiy|2aiy]], [[2hiu|2hiu]], [[3aiy|3aiy]], [[4aiy|4aiy]], [[5aiy|5aiy]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uz9 OCA], [http://pdbe.org/1uz9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1uz9 RCSB], [http://www.ebi.ac.uk/pdbsum/1uz9 PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[http://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref>   Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[http://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref>   Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[http://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref>   Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[http://omim.org/entry/613370 613370]]. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The addition of specific bulky hydrophobic groups to the insulin molecule provides it with affinity for circulating serum albumin and enables it to form soluble macromolecular complexes at the site of subcutaneous injection, thereby securing slow absorption of the insulin analogue into the blood stream and prolonging its half-life once there. N-Lithocholic acid acylated insulin [Lys(B29)-lithocholyl des-(B30) human insulin] has been crystallized and the structure determined by X-ray crystallography at 1.6 A resolution to explore the molecular basis of its assembly. The unit cell in the crystal consists of an insulin hexamer containing two zinc ions, with two m-cresol molecules bound at each dimer-dimer interface stabilizing an R(6) conformation. Six covalently bound lithocholyl groups are arranged symmetrically around the outside of the hexamer. These form specific van der Waals and hydrogen-bonding interactions at the interfaces between neighboring hexamers, possibly representing the kinds of interactions which occur in the soluble aggregates at the site of injection. Comparison with an equivalent nonderivatized native insulin hexamer shows that the addition of the lithocholyl group disrupts neither the important conformational features of the insulin molecule nor its hexamer-forming ability. Indeed, binding studies show that the affinity of N-lithocholyl insulin for the human insulin receptor is not significantly diminished.

Crystallographic and solution studies of N-lithocholyl insulin: a new generation of prolonged-acting human insulins.,Whittingham JL, Jonassen I, Havelund S, Roberts SM, Dodson EJ, Verma CS, Wilkinson AJ, Dodson GG Biochemistry. 2004 May 25;43(20):5987-95. PMID:15147182<ref>PMID:15147182</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1uz9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Molecular Playground/Insulin|Molecular Playground/Insulin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dodson, E J]]
[[Category: Dodson, G G]]
[[Category: Havelund, S]]
[[Category: Jonassen, I]]
[[Category: Roberts, S M]]
[[Category: Verma, C S]]
[[Category: Whittingham, J L]]
[[Category: Wilkinson, A J]]
[[Category: Diabetes mellitus]]
[[Category: Hormone disease mutation]]
[[Category: Insulin]]
[[Category: Insulin family]]