Human glucose-6-phosphate isomerase(GPI) or phosphoglucose isomerase(PGI)

Human glucose-6-phosphate isomerase (GPI) or phosphoglucose isomerase (PGI)
1. Introduction
2. Structure
3. 3D Crystal Structure
4. Functions
5. Catalytic mechanism
6. References

1. Presented by: Ayesha Kabeer Topic: Human Glucose-6-phosphate isomerase University of Gujrat Sialkot Sub campus

2. Table of contents: Human glucose-6-phosphate isomerase(GPI) or phosphoglucose isomerase(PGI) Introduction Structure 3D Crystal Structure Functions Catalytic mechanism References

3. Human Glucose-6-phosphate isomerase: Introduction. Human Glucose-6-phosphate isomerase, alternatively known as phosphoglucose isomerase, is an enzyme that in humans is encoded by the GPI gene on chromosome 19. An enzyme which interconverts glucose-6-phosphate and fructose-6-phosphate. ENZYME COMMISSION NUMBER : 5.3.1.9 PDB ID: 1JLH SUBSTRATES: glucose-6-phosphate(G6P) fructose-6-phosphate(F6P)

4. Human Glucose-6-phosphate isomerase: Structure. AMINO ACID RESIDUES LENGTH: 558 AMINO ACID CHAINS: CHAIN A: CHAIN A1, A2, A3 CHAIN B: CHAIN B1, B2, B3 CHAIN C: CHAIN C1, C2, C3 CHAIN D: CHAIN D1, D2, D3 ∝- helices: 37 β- sheets: 21 RESOLUTION OF PGI STRUCTURE: 2.1Å MOLECULAR WEIGHT : approx. 200,000Da OPTIMUM pH : 9.0 - 10.0 pH STABILITY : 6.0 - 10.5 ISOELECTRIC POINT : 4.2

5. Human Glucose-6-phosphate isomerase: 3D Crystal Structure.

6. Human Glucose-6-phosphate isomerase: Functions. Molecular function: Cytokine activity Growth factor activity Intramolecular transferase activity Ubiquitin protein ligase binding Monosaccharide binding

7. Human Glucose-6-phosphate isomerase: Functions. Biological processes: Angiogenesis Carbohydrate Metabolic Process Gluconeogenesis Glycolytic Process Hemostasis Aldehyde Catabolic Process Glucose Homeostasis

8. Human Glucose-6-phosphate isomerase: Catalytic Mechanism. The isomerization reaction of PGI proceeds by a general acid/base catalysis. His388 and Lys518 are involved in the sugar ring opening process, whereas, Glu357 is the base responsible for proton abstraction from the C1 and C2 positions of fructose 6-phosphate and glucose 6-phosphate respectively. After substrate (sugar ring i.e. G6P or F6P) binding to enzyme, the first step is the sugar ring opening, which is basically catalyzed by the acid group of Lys518 residue (i.e. acid catalysis). In this step, NH 3 + of lysine residue donates a proton to sugar ring oxygen to open the ring.

9. Human Glucose-6-phosphate isomerase: Catalytic Mechanism. This results in the loss of a proton from C1 hydroxyl group in case of glucose-6-phosphate or C2 hydroxyl group in case of fructose-6-phoshate to the solvent and a carbonyl group is formed at C1 position of G6P or C2 position of F6P. Glu357 then abstracts a proton from the C2 position of G6P or C1 position of F6P (i.e. base catalysis), causing electrons to flow towards the C1 carbonyl of G6P or C2 carbonyl of F6P. The resulting negative charge attracts a proton from the solvent, forming the cis-enediol intermediate. Glu357 then donates back a proton (i.e. acid catalysis) to the C1 position (in case of G6P) or C2 position (in case of F6P).

10. Human Glucose-6-phosphate isomerase: Catalytic Mechanism. The resulting electron flow towards Glu357 leaves a carbonyl group at C2 of G6P or C1 of F6P. In the last step Lys518 (or His388) abstracts a proton (i.e. base catalysis) from the sugar ring oxygen leading to ring closure and the reestablishment of a hydroxyl group at C2 or C1. And through the series of these reversible steps, G6P is converted into F6P or F6P is converted into G6P by the enzyme PGI (i.e. phosphoglucose isomerase).

11. Catalytic mechanism of PGI

12. References: Read, Jon, Pearce, Jake, Li, Xiaochun, Muirhead, Hilary, Chirgwin, John, & Davies, Christopher. (2001). The crystal structure of human phosphoglucose isomerase at 1.6 Å resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia. Journal of molecular biology, 309 (2), 447-463. Rose, Alexander S, & Hildebrand, Peter W. (2015). NGL Viewer: a web application for molecular visualization. Nucleic acids research, 43 (W1), W576-W579. Rose, Peter W, Prlić, Andreas, Altunkaya, Ali, Bi, Chunxiao, Bradley, Anthony R, Christie, Cole H, . . . Feng, Zukang. (2016). The RCSB protein data bank: integrative view of protein, gene and 3D structural information. Nucleic acids research , gkw1000.