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7rm9

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Human Malate Dehydrogenase I (MDHI)

Structural highlights

7rm9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.65Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MDHC_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

MDHC_HUMAN Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237).^[1] ^[2]

Publication Abstract from PubMed

The first crystal structure of the human cytosolic malate dehydrogenase I (MDH1) is described. Structure determination at a high resolution (1.65 A) followed production, isolation, and purification of human MDH1 using a bacterial expression system. The structure is a binary complex of MDH1 with only a bound malonate molecule in the substrate binding site. Comparisons of this structure with malate dehydrogenase enzymes from other species confirm that the human enzyme adopts similar secondary, tertiary, and quaternary structures and that the enzyme retains a similar conformation even when nicotinamide adenine dinucleotide (NAD(+)) is not bound. A comparison to the highly homologous porcine (sus scrofa) MDH1 ternary structures leads to the conclusion that only small conformational differences are needed to accommodate binding by NAD(+) or other NAD(+) mimetics. Conformational differences observed in the second subunit show that the NAD(+) binding elements are nevertheless quite flexible. Comparison of hMDH1 to the human mitochondrial malate dehydrogenase (hMDH2) reveals some key differences in the alpha7-alpha8 loop, which lies directly beneath the substrate binding pocket. These differences might be exploited in the structure-assisted design of selective small molecule inhibitors of hMDH1, an emerging target for the development of anticancer therapeutics.

Structural Characterization of the Human Cytosolic Malate Dehydrogenase I.,McCue WM, Finzel BC ACS Omega. 2021 Dec 28;7(1):207-214. doi: 10.1021/acsomega.1c04385. eCollection, 2022 Jan 11. PMID:35036692^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Friedrich CA, Ferrell RE, Siciliano MJ, Kitto GB. Biochemical and genetic identity of alpha-keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes. Ann Hum Genet. 1988 Jan;52(1):25-37. doi: 10.1111/j.1469-1809.1988.tb01075.x. PMID:3052244 doi:http://dx.doi.org/10.1111/j.1469-1809.1988.tb01075.x
↑ Broeks MH, Shamseldin HE, Alhashem A, Hashem M, Abdulwahab F, Alshedi T, Alobaid I, Zwartkruis F, Westland D, Fuchs S, Verhoeven-Duif NM, Jans JJM, Alkuraya FS. MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle associated with early onset severe encephalopathy. Hum Genet. 2019 Dec;138(11-12):1247-1257. doi: 10.1007/s00439-019-02063-z. Epub, 2019 Sep 19. PMID:31538237 doi:http://dx.doi.org/10.1007/s00439-019-02063-z
↑ McCue WM, Finzel BC. Structural Characterization of the Human Cytosolic Malate Dehydrogenase I. ACS Omega. 2021 Dec 28;7(1):207-214. doi: 10.1021/acsomega.1c04385. eCollection, 2022 Jan 11. PMID:35036692 doi:http://dx.doi.org/10.1021/acsomega.1c04385

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7rm9"

Categories: Homo sapiens | Large Structures | Finzel BC | McCue W

@@ Line 3: / Line 3: @@
 <StructureSection load='7rm9' size='340' side='right'caption='[[7rm9]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7rm9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RM9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7rm9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RM9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7rm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rm9 OCA], [https://pdbe.org/7rm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rm9 RCSB], [https://www.ebi.ac.uk/pdbsum/7rm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rm9 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/MDHC_HUMAN MDHC_HUMAN]] The disease is caused by variants affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/MDHC_HUMAN MDHC_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
 == Function ==
-[[https://www.uniprot.org/uniprot/MDHC_HUMAN MDHC_HUMAN]] Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237).<ref>PMID:3052244</ref> <ref>PMID:31538237</ref>
+[https://www.uniprot.org/uniprot/MDHC_HUMAN MDHC_HUMAN] Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237).<ref>PMID:3052244</ref> <ref>PMID:31538237</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 7rm9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Malate Dehydrogenase 3D structures|Malate Dehydrogenase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Finzel, B C]]
+[[Category: Finzel BC]]
-[[Category: McCue, W]]
+[[Category: McCue W]]
-[[Category: Oxidoreductase]]

7rm9

From Proteopedia

Current revision

Human Malate Dehydrogenase I (MDHI)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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