2xe8
From Proteopedia
The complete reaction cycle of human phosphoglycerate kinase: The open ternary complex with 3PG and AMP-PNP
Structural highlights
Disease[PGK1_HUMAN] Defects in PGK1 are the cause of phosphoglycerate kinase 1 deficiency (PGK1D) [MIM:300653]. It is a condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations.[1] [2] [3] [4] [5] [6] [7] [8] [9] Function[PGK1_HUMAN] In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein). Publication Abstract from PubMedPhosphoglycerate kinase (PGK) is the enzyme responsible for the first ATP-generating step of glycolysis and has been implicated extensively in oncogenesis and its development. Solution small angle x-ray scattering (SAXS) data, in combination with crystal structures of the enzyme in complex with substrate and product analogues, reveal a new conformation for the resting state of the enzyme and demonstrate the role of substrate binding in the preparation of the enzyme for domain closure. Comparison of the x-ray scattering curves of the enzyme in different states with crystal structures has allowed the complete reaction cycle to be resolved both structurally and temporally. The enzyme appears to spend most of its time in a fully open conformation with short periods of closure and catalysis, thereby allowing the rapid diffusion of substrates and products in and out of the binding sites. Analysis of the open apoenzyme structure, defined through deformable elastic network refinement against the SAXS data, suggests that interactions in a mostly buried hydrophobic region may favor the open conformation. This patch is exposed on domain closure, making the open conformation more thermodynamically stable. Ionic interactions act to maintain the closed conformation to allow catalysis. The short time PGK spends in the closed conformation and its strong tendency to rest in an open conformation imply a spring-loaded release mechanism to regulate domain movement, catalysis, and efficient product release. A Spring-loaded Release Mechanism Regulates Domain Movement and Catalysis in Phosphoglycerate Kinase.,Zerrad L, Merli A, Schroder GF, Varga A, Graczer E, Pernot P, Round A, Vas M, Bowler MW J Biol Chem. 2011 Apr 22;286(16):14040-8. Epub 2011 Feb 24. PMID:21349853[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||||
Categories: Human | Large Structures | Phosphoglycerate kinase | Baxter, N J | Blackburn, G M | Bowler, M W | Cliff, M J | Merli, A | Vas, M | Waltho, J P | Domain motion | Glycolysis | Hereditary hemolytic anemia | Kinase | Nucleotide-binding | Phosphoprotein | Phosphoryl transfer | Transferase | Transition state analogue
