1f3x: Difference between revisions

|PDB= 1f3x |SIZE=350|CAPTION= <scene name='initialview01'>1f3x</scene>, resolution 2.80&Aring;

|SITE=  

|LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene>

|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </span>

|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f3x OCA], [http://www.ebi.ac.uk/pdbsum/1f3x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1f3x RCSB]</span>

==Overview==

Mammalian pyruvate kinase (PK) is a four-domain enzyme that is active as a homo-tetramer. Tissue-specific isozymes of PK exhibit distinct levels of allosteric regulation. PK expressed in muscle tissue (M1-PK) shows hyperbolic steady-state kinetics, whereas PK expressed in kidney tissue (M2-PK) displays sigmoidal kinetics. Rabbit M1 and M2-PK are isozymes whose sequences differ in only 22 out of 530 residues per subunit, and these changes are localized in an inter-subunit interface. Previous studies have shown that a single amino acid mutation to M1-PK at either the Y (S402P) or Z (T340 M) subunit interface can confer a level of allosteric regulation that is intermediate to M1-PK and M2-PK. In an effort to elucidate the roles of the inter-subunit interaction in signal transmission and the functional/structural connectivity between these interfaces, the S402P mutant of M1-PK was crystallized and its structure resolved to 2.8 A. Although the overall S402P M1-PK structure is nearly identical with the wild-type structure within experimental error, significant differences in the conformation of the backbone are found at the site of mutation along the Y interface. In addition, there is a significant change along the Z interface, namely, a loss of an inter-subunit salt-bridge between Asp177 of domain B and Arg341 of domain A of the opposing subunit. Concurrent with the loss of the salt-bridge is an increase in the degree of rotational flexibility of domain B that constitutes the active site. Comparison of previous PK structures shows a correlation between an increase in this domain movement with the loss of the Asp177: Arg341 salt-bridge. These results identify the structural linkages between the Y and Z interfaces in regulating the interconversion of conformational states of rabbit M1-PK.

 

==About this Structure==

1F3X is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F3X OCA].

 

Structural and functional linkages between subunit interfaces in mammalian pyruvate kinase., Wooll JO, Friesen RH, White MA, Watowich SJ, Fox RO, Lee JC, Czerwinski EW, J Mol Biol. 2001 Sep 21;312(3):525-40. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11563914 11563914]

[[Category: Czerwinski, E W.]]

[[Category: Fox, R O.]]

[[Category: Friesen, R H.E.]]

[[Category: Lee, J C.]]

[[Category: Watowich, S J.]]

[[Category: White, M A.]]

[[Category: Wooll, J O.]]

[[Category: muscle isozyme]]

[[Category: pyruvate kinase]]