A clinical mutation in glucokinase causing maturity-onset diabetes in the young type 2 increases enzyme activity
© 2022 Federation of European Biochemical Societies..
Glucokinase (GCK) is the pancreatic β-cell glucose sensor, and its kinetics are key to that purpose. A slow transition step, displayed as non-hyperbolic kinetics, and a low affinity for glucose characterize GCK. Mutations in GCK associated with maturity-onset diabetes of the young type 2 (MODY2) previously described reduce the functionality of the human pancreatic β-cell, leading to diabetic clinical phenotypes. We present a kinetic characterization of the G448D mutation identified in a MODY2 patient, which is one of the first mutations to exhibit increased functionality. This mutant displays increased activity, high affinity for both Mg2+ -ATP and glucose, hyperbolic kinetics and increased phosphorylation potential. Hyperbolic kinetics and assays in the presence of glycerol indicate that G448D lacks the slow transition step crucial for the pancreatic β-cell glucose sensor function.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:597 |
|---|---|
| Enthalten in: |
FEBS letters - 597(2023), 11 vom: 01. Juni, Seite 1469-1478 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Aránguiz, Oscar [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
EC 2.7.1.2 |
|---|
| Anmerkungen: |
Date Completed 14.06.2023 Date Revised 15.06.2023 published: Print-Electronic RefSeq: NM_000162.4 Citation Status MEDLINE |
|---|
| doi: |
10.1002/1873-3468.14561 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM350324271 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM350324271 | ||
| 003 | DE-627 | ||
| 005 | 20231226044736.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/1873-3468.14561 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1167.xml |
| 035 | |a (DE-627)NLM350324271 | ||
| 035 | |a (NLM)36520489 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Aránguiz, Oscar |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A clinical mutation in glucokinase causing maturity-onset diabetes in the young type 2 increases enzyme activity |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.06.2023 | ||
| 500 | |a Date Revised 15.06.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a RefSeq: NM_000162.4 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 Federation of European Biochemical Societies. | ||
| 520 | |a Glucokinase (GCK) is the pancreatic β-cell glucose sensor, and its kinetics are key to that purpose. A slow transition step, displayed as non-hyperbolic kinetics, and a low affinity for glucose characterize GCK. Mutations in GCK associated with maturity-onset diabetes of the young type 2 (MODY2) previously described reduce the functionality of the human pancreatic β-cell, leading to diabetic clinical phenotypes. We present a kinetic characterization of the G448D mutation identified in a MODY2 patient, which is one of the first mutations to exhibit increased functionality. This mutant displays increased activity, high affinity for both Mg2+ -ATP and glucose, hyperbolic kinetics and increased phosphorylation potential. Hyperbolic kinetics and assays in the presence of glycerol indicate that G448D lacks the slow transition step crucial for the pancreatic β-cell glucose sensor function | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hill coefficient | |
| 650 | 4 | |a MODY2 | |
| 650 | 4 | |a glucokinase | |
| 650 | 4 | |a kinetic parameters | |
| 650 | 4 | |a mutation | |
| 650 | 7 | |a Glucokinase |2 NLM | |
| 650 | 7 | |a EC 2.7.1.2 |2 NLM | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 700 | 1 | |a Rivera, Rodrigo |e verfasserin |4 aut | |
| 700 | 1 | |a Durruty, Pilar |e verfasserin |4 aut | |
| 700 | 1 | |a Seelenfreund, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Báez, Mauricio |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t FEBS letters |d 1968 |g 597(2023), 11 vom: 01. Juni, Seite 1469-1478 |w (DE-627)NLM000016691 |x 1873-3468 |7 nnns |
| 773 | 1 | 8 | |g volume:597 |g year:2023 |g number:11 |g day:01 |g month:06 |g pages:1469-1478 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/1873-3468.14561 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 597 |j 2023 |e 11 |b 01 |c 06 |h 1469-1478 | ||