Vascular Endothelial Growth Factor - Revision history

Michal Harel at 08:45, 22 January 2023

Michal Harel — Sun, 22 Jan 2023 08:45:01 GMT

←Older revision		Revision as of 08:45, 22 January 2023
Line 7:		Line 7:
	[[VEGFR]]<br />		[[VEGFR]]<br />
	[[VEGF IN COMPLEX WITH A NEUTRALIZING ANTIBODY]]<br />		[[VEGF IN COMPLEX WITH A NEUTRALIZING ANTIBODY]]<br />
-	[[Autocrine signaling]]	+	[[Autocrine signaling]]<br />
	[[VEGF signaling pathway]].		[[VEGF signaling pathway]].
	<br />		<br />

Michal Harel at 08:44, 22 January 2023

Michal Harel — Sun, 22 Jan 2023 08:44:16 GMT

←Older revision		Revision as of 08:44, 22 January 2023
Line 7:		Line 7:
	[[VEGFR]]<br />		[[VEGFR]]<br />
	[[VEGF IN COMPLEX WITH A NEUTRALIZING ANTIBODY]]<br />		[[VEGF IN COMPLEX WITH A NEUTRALIZING ANTIBODY]]<br />
-	[[Autocrine signaling]].	+	[[Autocrine signaling]]
		+	[[VEGF signaling pathway]].
	<br />		<br />
	<br />		<br />

Michal Harel at 10:27, 5 January 2023

Michal Harel — Thu, 05 Jan 2023 10:27:52 GMT

←Older revision		Revision as of 10:27, 5 January 2023
Line 6:		Line 6:
	[[Vascular Endothelial Growth Factor]]s (VEGFs) are a class of proteins that regulate vascular development in embryos and angiogenesis in adult mammals after sustaining an injury or notably in [[Cancer\|cancerous]] tumors. A number of structural studies have been conducted on VEGF and its receptors (VEGFRs) to better understand the VEGF-VEGFR interaction and how the signal cascade originating from this interaction leads to a number of biological features. VEGF and its receptors have been closely looked at for their potential use as targets for pharmaceutical medicine with some success. The VEGF family contains VEGF-A which mediates increased vascular permeability, VEGF-B which is a growth factor, VEGF-C is active in angiogenesis, VEGF-E is found in viruses and VEGF-F in snake venom.<br /> For additional information see:<br />		[[Vascular Endothelial Growth Factor]]s (VEGFs) are a class of proteins that regulate vascular development in embryos and angiogenesis in adult mammals after sustaining an injury or notably in [[Cancer\|cancerous]] tumors. A number of structural studies have been conducted on VEGF and its receptors (VEGFRs) to better understand the VEGF-VEGFR interaction and how the signal cascade originating from this interaction leads to a number of biological features. VEGF and its receptors have been closely looked at for their potential use as targets for pharmaceutical medicine with some success. The VEGF family contains VEGF-A which mediates increased vascular permeability, VEGF-B which is a growth factor, VEGF-C is active in angiogenesis, VEGF-E is found in viruses and VEGF-F in snake venom.<br /> For additional information see:<br />
	[[VEGFR]]<br />		[[VEGFR]]<br />
-	[[VEGF IN COMPLEX WITH A NEUTRALIZING ANTIBODY]]..	+	[[VEGF IN COMPLEX WITH A NEUTRALIZING ANTIBODY]]<br />
		+	[[Autocrine signaling]].
	<br />		<br />
	<br />		<br />

Michal Harel at 09:24, 25 March 2020

Michal Harel — Wed, 25 Mar 2020 09:24:18 GMT

←Older revision		Revision as of 09:24, 25 March 2020
Line 44:		Line 44:
	</StructureSection>		</StructureSection>
	{{Clear}}		{{Clear}}
-	== 3D Structures of VEGF==

-	Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-	{{#tree:id=OrganizedByTopic\|openlevels=0\|
-
-	*VEGF-A; Domains - receptor-binding domain 27-135; heparin-binding domain 137-191
-
-	**[[5hhc]], [[5hhd]] – hVEGF-A 214-315 - human <br />
-	**[[1mkg]], [[1mkk]], [[1mjv]] – hVEGF-A receptor-binding domain (mutant) <br />
-	**[[3bdy]], [[2qr0]] - hVEGF-A receptor-binding domain + hFab light+heavy chain <br />
-	**[[4kzn]], [[3qtk]], [[2vpf]], [[1vpf]] - hVEGF-A receptor-binding domain<br />
-	**[[2fjg]], [[2fjh]] - hVEGF-A receptor-binding domain + hFab light+heavy chain <br />
-	**[[3p9w]] - hVEGF-A receptor-binding domain + hFab heavy chain<br />
-	**[[5fv1]], [[5fv2]] – hVEGF-A receptor-binding domain + antibody residues 1-108<br />
-	**[[4zff]], [[6bft]] - hVEGF-A residues 217-315 + hFab light+heavy chain<br />
-	**[[1tzh]], [[1tzi]], [[1cz8]] - hVEGF-A receptor-binding domain + mFab YADS1 light+heavy chain - mouse<br />
-	**[[5o4e]] – hVEGF-A receptor-binding domain (mutant) + IgG γ-1<br />
-	**[[4glu]] - hVEGF-A receptor-binding domain<br />
-	**[[1kmx]] - hVEGF-A heparin-binding domain<br />
-	**[[1vgh]], [[2vgh]] - hVEGF-A heparin-binding domain - NMR<br />
-	**[[1qty]], [[1flt]] – hVEGF-A receptor-binding domain + hFMS-like tyrosine <br />
-	**[[1vpp]] – hVEGF-A receptor-binding domain + receptor blocking peptide <br />
-	**[[6d3o]] – hVEGF-A receptor-binding domain + HH4 peptide <br />
-	**[[1bj1]] – hVEGF-A receptor-binding domain + mFab light+heavy chain fragments <br />
-	**[[1kat]] - hVEGF-A receptor binding domain + peptide antagonist - NMR<br />
-	**[[3s1b]] - hVEGF-A receptor-binding domain + Mini-Z<br />
-	**[[3s1k]] - hVEGF-A receptor-binding domain + Z-domain<br />
-	**[[4gln]], [[4gls]] - hVEGF-A receptor-binding domain + D-RFX001<br />
-	**[[4deq]] – hVEGF-A /neuropilin-1<br />
-	**[[4qaf]] – hVEGF-A receptor-binding domain + lipocalin-1<br />
-	**[[4wpb]] – hVEGF-A 214-315 + α/βVEGF<br />
-	**[[5hhc]], [[5hhd]] – hVEGF-A heterochiral 214-315<br />
-	**[[5t89]] – hVEGF-A receptor-binding domain+ VEGFR1 <br />
-
-	*VEGF-B
-
-	**[[2xac]] – hVEGF-B receptor binding domain+ hVEGFR domain 2<br />
-	**[[2vwe]] – hVEGF-B + mFab light+heavy chain fragments <br />
-	**[[2c7w]] – hVEGF-B <br />
-	**[[3v2a]] – hVEGF-B + VEGF-A<br />
-
-	*VEGF-C
-
-	**[[2x1w]], [[2x1x]] – hVEGF-C VEGF homology domain+ VEGFR-2 domains 2 & 3<br />
-	**[[4bsk]] - hVEGF-C VEGF homology domain + VEGFR-3 domains 1 & 2<br />
-
-	*VEGF-D
-
-	**[[2xv7]] – hVEGF-D VEGF homology domain
-
-	*VEGF-E
-
-	**[[2gnn]] – VEGF-E – Orf virus<br />
-	**[[3v6b]] – VEGF-E + VEGFR 2 <br />
-
-	*VEGF-F
-
-	**[[1wq8]], [[1wq9]] - VEGF-F – ''Vipera aspis''
-	}}
	==Additional Resources==		==Additional Resources==
	For additional information, see:		For additional information, see:
Line 111:		Line 53:
	==References==		==References==
	<references />		<references />
-

	[[Category:Topic Page]]		[[Category:Topic Page]]

Michal Harel at 09:23, 25 March 2020

Michal Harel — Wed, 25 Mar 2020 09:23:00 GMT

←Older revision		Revision as of 09:23, 25 March 2020
Line 40:		Line 40:
	VEGF has received significant attention from the pharmaceutical industry in the hopes of correcting impaired vessel function. Such impaired vessel function accompanies many pathologies including atherosclerosis, arthritis, some neurodegenerative diseases such as ALS, and malignant cell growth such as cancerous tumors. <ref> PMID:15488020</ref> In fact, numerous studies highlighted the increased expression of VEGF in cancer cells resulting in tumoral angiogenesis, providing the tumor with the network of blood vessels need to grow and expand. VEGF expression is stimulated by hypoxia, a common characteristic of most newly formed tumors, and genetic mutations such as [[K-ras]] and [[p53]], extremely common mutations present in a majority of cancers. <ref>PMID:20662002</ref> Since angiogenesis in typical adults is infrequent while extremely common in tumors, VEGF serves as a selective therapeutic target for cancer. A number of drugs, like Bevacizumab (a [[monoclonal antibody]] better known as [[Avastin]]) have been developed to interrupt the VEGF-VEGFR connection, with some success. Avastin binds to and inhibits all VEGF-A isoforms and has achieved megablockbuster status by earning over $5 billion in 2009 for Roche. <ref>http://www.foxbusiness.com/story/markets/industries/technology/roche-increased-avastin-sales-efforts-doubles-force/</ref>		VEGF has received significant attention from the pharmaceutical industry in the hopes of correcting impaired vessel function. Such impaired vessel function accompanies many pathologies including atherosclerosis, arthritis, some neurodegenerative diseases such as ALS, and malignant cell growth such as cancerous tumors. <ref> PMID:15488020</ref> In fact, numerous studies highlighted the increased expression of VEGF in cancer cells resulting in tumoral angiogenesis, providing the tumor with the network of blood vessels need to grow and expand. VEGF expression is stimulated by hypoxia, a common characteristic of most newly formed tumors, and genetic mutations such as [[K-ras]] and [[p53]], extremely common mutations present in a majority of cancers. <ref>PMID:20662002</ref> Since angiogenesis in typical adults is infrequent while extremely common in tumors, VEGF serves as a selective therapeutic target for cancer. A number of drugs, like Bevacizumab (a [[monoclonal antibody]] better known as [[Avastin]]) have been developed to interrupt the VEGF-VEGFR connection, with some success. Avastin binds to and inhibits all VEGF-A isoforms and has achieved megablockbuster status by earning over $5 billion in 2009 for Roche. <ref>http://www.foxbusiness.com/story/markets/industries/technology/roche-increased-avastin-sales-efforts-doubles-force/</ref>
	<br />		<br />
-		+	== 3D Structures of VEGF==
		+	[[VEGF 3D Structures]]
	</StructureSection>		</StructureSection>
	{{Clear}}		{{Clear}}
Line 48:		Line 49:
	{{#tree:id=OrganizedByTopic\|openlevels=0\|		{{#tree:id=OrganizedByTopic\|openlevels=0\|

-	*VEGF-A	+	*VEGF-A; Domains - receptor-binding domain 27-135; heparin-binding domain 137-191

-	**[[5hhc]], [[5hhd]] – hVEGF-A - human <br />	+	**[[5hhc]], [[5hhd]] – hVEGF-A 214-315 - human <br />
-	**[[1mkg]], [[1mkk]], [[1mjv]] – hVEGF-A (mutant) <br />	+	**[[1mkg]], [[1mkk]], [[1mjv]] – hVEGF-A receptor-binding domain (mutant) <br />
-	**[[3bdy]], [[2qr0]] - hVEGF-A + hFab light+heavy chain <br />	+	**[[3bdy]], [[2qr0]] - hVEGF-A receptor-binding domain + hFab light+heavy chain <br />
	**[[4kzn]], [[3qtk]], [[2vpf]], [[1vpf]] - hVEGF-A receptor-binding domain<br />		**[[4kzn]], [[3qtk]], [[2vpf]], [[1vpf]] - hVEGF-A receptor-binding domain<br />
-	**[[2fjg]], [[2fjh]] - hVEGF-A receptor-binding domain+ hFab light+heavy chain <br />	+	**[[2fjg]], [[2fjh]] - hVEGF-A receptor-binding domain + hFab light+heavy chain <br />
-	**[[3p9w]] - hVEGF-A + hFab heavy chain<br />	+	**[[3p9w]] - hVEGF-A receptor-binding domain + hFab heavy chain<br />
	**[[5fv1]], [[5fv2]] – hVEGF-A receptor-binding domain + antibody residues 1-108<br />		**[[5fv1]], [[5fv2]] – hVEGF-A receptor-binding domain + antibody residues 1-108<br />
-	**[[4zff]] - hVEGF-A residues 217-315 + hFab light+heavy chain<br />	+	**[[4zff]], [[6bft]] - hVEGF-A residues 217-315 + hFab light+heavy chain<br />
-	**[[1tzh]], [[1tzi]], [[1cz8]] - hVEGF-A + mFab YADS1 light+heavy chain - mouse<br />	+	**[[1tzh]], [[1tzi]], [[1cz8]] - hVEGF-A receptor-binding domain + mFab YADS1 light+heavy chain - mouse<br />
-	**[[5o4e]] – hVEGF-A (mutant) + IgG γ-1<br />	+	**[[5o4e]] – hVEGF-A receptor-binding domain (mutant) + IgG γ-1<br />
-	**[[4glu]] - hVEGF-A ~~residues 1~~-~~102~~<br />	+	**[[4glu]] - hVEGF-A receptor-binding domain<br />
	**[[1kmx]] - hVEGF-A heparin-binding domain<br />		**[[1kmx]] - hVEGF-A heparin-binding domain<br />
	**[[1vgh]], [[2vgh]] - hVEGF-A heparin-binding domain - NMR<br />		**[[1vgh]], [[2vgh]] - hVEGF-A heparin-binding domain - NMR<br />
	**[[1qty]], [[1flt]] – hVEGF-A receptor-binding domain + hFMS-like tyrosine <br />		**[[1qty]], [[1flt]] – hVEGF-A receptor-binding domain + hFMS-like tyrosine <br />
-	**[[1vpp]] – hVEGF-A + receptor blocking peptide <br />	+	**[[1vpp]] – hVEGF-A receptor-binding domain + receptor blocking peptide <br />
-	**[[1bj1]] – hVEGF-A + mFab light+heavy chain fragments <br />	+	**[[6d3o]] – hVEGF-A receptor-binding domain + HH4 peptide <br />
		+	**[[1bj1]] – hVEGF-A receptor-binding domain + mFab light+heavy chain fragments <br />
	**[[1kat]] - hVEGF-A receptor binding domain + peptide antagonist - NMR<br />		**[[1kat]] - hVEGF-A receptor binding domain + peptide antagonist - NMR<br />
-	**[[3s1b]] - hVEGF-A + Mini-Z<br />	+	**[[3s1b]] - hVEGF-A receptor-binding domain + Mini-Z<br />
-	**[[3s1k]] - hVEGF-A + Z-domain<br />	+	**[[3s1k]] - hVEGF-A receptor-binding domain + Z-domain<br />
-	**[[4gln]], [[4gls]] - hVEGF-A + D-RFX001<br />	+	**[[4gln]], [[4gls]] - hVEGF-A receptor-binding domain + D-RFX001<br />
	**[[4deq]] – hVEGF-A /neuropilin-1<br />		**[[4deq]] – hVEGF-A /neuropilin-1<br />
-	**[[4qaf]] – hVEGF-A + lipocalin-1<br />	+	**[[4qaf]] – hVEGF-A receptor-binding domain + lipocalin-1<br />
-	**[[4wpb]] – hVEGF-A + α/βVEGF<br />	+	**[[4wpb]] – hVEGF-A 214-315 + α/βVEGF<br />
-	**[[5hhc]], [[5hhd]] – hVEGF-A heterochiral<br />	+	**[[5hhc]], [[5hhd]] – hVEGF-A heterochiral 214-315<br />
-	**[[5t89]] – hVEGF-A + VEGFR1 <br />	+	**[[5t89]] – hVEGF-A receptor-binding domain+ VEGFR1 <br />

	*VEGF-B		*VEGF-B

Michal Harel at 20:45, 5 October 2018

Michal Harel — Fri, 05 Oct 2018 20:45:56 GMT

←Older revision		Revision as of 20:45, 5 October 2018
Line 1:		Line 1:
-	<StructureSection load='.pdb' size='~~400~~' side='right' scene='Vascular_Endothelial_Growth_Factor/Vegf-a_opening/1' caption='Structure of Human VEGF-A dimer, [[1vpf]]'>	+	<StructureSection load='.pdb' size='350' side='right' scene='Vascular_Endothelial_Growth_Factor/Vegf-a_opening/1' caption='Structure of Human VEGF-A dimer, [[1vpf]]'>
	[[Image: VEGF_Opening.png\|300px\|left\|thumb\| VEGF-A highlighting 2 monomers and binding sites in red, [[1vpf]]]]		[[Image: VEGF_Opening.png\|300px\|left\|thumb\| VEGF-A highlighting 2 monomers and binding sites in red, [[1vpf]]]]

Line 94:		Line 94:
	*VEGF-E		*VEGF-E

-	**[[3v6b]] – VEGF-E + VEGFR 2 ~~– Orf virus~~<br />	+	**[[2gnn]] – VEGF-E – Orf virus<br />
		+	**[[3v6b]] – VEGF-E + VEGFR 2 <br />

	*VEGF-F		*VEGF-F

Joel L. Sussman at 03:26, 16 October 2017

Joel L. Sussman — Mon, 16 Oct 2017 03:26:24 GMT

←Older revision		Revision as of 03:26, 16 October 2017
Line 1:		Line 1:
-	<StructureSection load='~~1vpf2~~.pdb' size='400' side='right' scene='Vascular_Endothelial_Growth_Factor/Vegf-a_opening/1' caption='Structure of Human VEGF-A dimer, [[1vpf]]'>	+	<StructureSection load='.pdb' size='400' side='right' scene='Vascular_Endothelial_Growth_Factor/Vegf-a_opening/1' caption='Structure of Human VEGF-A dimer, [[1vpf]]'>
	[[Image: VEGF_Opening.png\|300px\|left\|thumb\| VEGF-A highlighting 2 monomers and binding sites in red, [[1vpf]]]]		[[Image: VEGF_Opening.png\|300px\|left\|thumb\| VEGF-A highlighting 2 monomers and binding sites in red, [[1vpf]]]]

Michal Harel at 22:51, 13 October 2017

Michal Harel — Fri, 13 Oct 2017 22:51:43 GMT

←Older revision		Revision as of 22:51, 13 October 2017
Line 50:		Line 50:
	*VEGF-A		*VEGF-A

-	**[[3bdy]], [[2qr0]] - hVEGF-A + hFab light+heavy chain ~~– human~~<br />	+	**[[5hhc]], [[5hhd]] – hVEGF-A - human <br />
		+	**[[1mkg]], [[1mkk]], [[1mjv]] – hVEGF-A (mutant) <br />
		+	**[[3bdy]], [[2qr0]] - hVEGF-A + hFab light+heavy chain <br />
	**[[4kzn]], [[3qtk]], [[2vpf]], [[1vpf]] - hVEGF-A receptor-binding domain<br />		**[[4kzn]], [[3qtk]], [[2vpf]], [[1vpf]] - hVEGF-A receptor-binding domain<br />
	**[[2fjg]], [[2fjh]] - hVEGF-A receptor-binding domain+ hFab light+heavy chain <br />		**[[2fjg]], [[2fjh]] - hVEGF-A receptor-binding domain+ hFab light+heavy chain <br />
Line 57:		Line 59:
	**[[4zff]] - hVEGF-A residues 217-315 + hFab light+heavy chain<br />		**[[4zff]] - hVEGF-A residues 217-315 + hFab light+heavy chain<br />
	**[[1tzh]], [[1tzi]], [[1cz8]] - hVEGF-A + mFab YADS1 light+heavy chain - mouse<br />		**[[1tzh]], [[1tzi]], [[1cz8]] - hVEGF-A + mFab YADS1 light+heavy chain - mouse<br />
-	**[[~~1mkg]], [[1mkk]], [[1mjv~~]] – hVEGF-A (mutant) <br />	+	**[[5o4e]] – hVEGF-A (mutant) + IgG γ-1<br />
	**[[4glu]] - hVEGF-A residues 1-102<br />		**[[4glu]] - hVEGF-A residues 1-102<br />
	**[[1kmx]] - hVEGF-A heparin-binding domain<br />		**[[1kmx]] - hVEGF-A heparin-binding domain<br />
Line 72:		Line 74:
	**[[4wpb]] – hVEGF-A + α/βVEGF<br />		**[[4wpb]] – hVEGF-A + α/βVEGF<br />
	**[[5hhc]], [[5hhd]] – hVEGF-A heterochiral<br />		**[[5hhc]], [[5hhd]] – hVEGF-A heterochiral<br />
		+	**[[5t89]] – hVEGF-A + VEGFR1 <br />

	*VEGF-B		*VEGF-B

Alexander Berchansky at 11:52, 18 January 2017

Alexander Berchansky — Wed, 18 Jan 2017 11:52:59 GMT

←Older revision		Revision as of 11:52, 18 January 2017
Line 30:		Line 30:
	<scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_opening/1'>VEGF-E</scene> consists of a homodimer that is covalently linked by two intermolecular disulfide bonds between <scene name='41/411433/Cys51-cys60/1'>Cys51 and Cys 60</scene>.		<scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_opening/1'>VEGF-E</scene> consists of a homodimer that is covalently linked by two intermolecular disulfide bonds between <scene name='41/411433/Cys51-cys60/1'>Cys51 and Cys 60</scene>.

-	Each monomer contains a central antiparallel beta sheet, with the canonical <scene name='41/411433/Knot_new/3'>cysteine knot </scene> found in other VEGFs. <ref>PMID:1396586</ref> The knot consists of an eight residue ring formed by the backbone of residues 57-61 and 102-104 and intramolecular disulfide bridges Cys57-Cys102 and Cys61-Cys104, and a third bridge, Cys26-Cys68, that passes perpendicularly through the ring. Each VEGF-E monomer contains an amino terminal alpha helix and three solvent accessible loop regions~~, L1~~, L2, ~~and L3~~ <scene name='41/411433/Vegf-e_l1_l3/2'>L1 and L3 </scene>.	+	Each monomer contains a central antiparallel beta sheet, with the canonical <scene name='41/411433/Knot_new/3'>cysteine knot </scene> found in other VEGFs. <ref>PMID:1396586</ref> The knot consists of an eight residue ring formed by the backbone of residues 57-61 and 102-104 and intramolecular disulfide bridges Cys57-Cys102 and Cys61-Cys104, and a third bridge, Cys26-Cys68, that passes perpendicularly through the ring. Each VEGF-E monomer contains an amino terminal alpha helix and three solvent accessible loop regions, L2, <scene name='41/411433/Vegf-e_l1_l3/3'>L1 and L3 </scene>.

	are able to form a complex hydrogen bond network as well as extensive hydrophobic contacts with VEGFR making these loops ideal receptor specificity determinants. Residues: P34, S36, T43, P50, R46, D63, E64, and E67 make up the <scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_binding_site/1'>VEGF-E binding pocket </scene>and are critical for binding to VEGFR-2 as determined by alanine mutagenesis.<ref> PMID:16672228</ref> Further, the salt bridge between <scene name='41/411433/Vegf-e_salt_bridge/4'>R46 and E64 </scene> is believed to be the source of VEGF-E’s VEGFR-2 specificity by preventing binding to VEGFR-1. <ref>PMID:15272021</ref>		are able to form a complex hydrogen bond network as well as extensive hydrophobic contacts with VEGFR making these loops ideal receptor specificity determinants. Residues: P34, S36, T43, P50, R46, D63, E64, and E67 make up the <scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_binding_site/1'>VEGF-E binding pocket </scene>and are critical for binding to VEGFR-2 as determined by alanine mutagenesis.<ref> PMID:16672228</ref> Further, the salt bridge between <scene name='41/411433/Vegf-e_salt_bridge/4'>R46 and E64 </scene> is believed to be the source of VEGF-E’s VEGFR-2 specificity by preventing binding to VEGFR-1. <ref>PMID:15272021</ref>

Joel L. Sussman at 17:34, 16 January 2017

Joel L. Sussman — Mon, 16 Jan 2017 17:34:09 GMT

←Older revision		Revision as of 17:34, 16 January 2017
Line 30:		Line 30:
	<scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_opening/1'>VEGF-E</scene> consists of a homodimer that is covalently linked by two intermolecular disulfide bonds between <scene name='41/411433/Cys51-cys60/1'>Cys51 and Cys 60</scene>.		<scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_opening/1'>VEGF-E</scene> consists of a homodimer that is covalently linked by two intermolecular disulfide bonds between <scene name='41/411433/Cys51-cys60/1'>Cys51 and Cys 60</scene>.

-	Each monomer contains a central antiparallel beta sheet, with the canonical <scene name='41/411433/Knot_new/2'>cysteine knot </scene> found in other VEGFs. <ref>PMID:1396586</ref> The knot consists of an eight residue ring formed by the backbone of residues 57-61 and 102-104 and intramolecular disulfide bridges Cys57-Cys102 and Cys61-Cys104, and a third bridge, Cys26-Cys68, that passes perpendicularly through the ring. Each VEGF-E monomer contains an amino terminal alpha helix and three solvent accessible loop regions, L1, L2, and L3 <scene name='41/411433/Vegf-e_l1_l3/2'>L1 and L3 </scene>.	+	Each monomer contains a central antiparallel beta sheet, with the canonical <scene name='41/411433/Knot_new/3'>cysteine knot </scene> found in other VEGFs. <ref>PMID:1396586</ref> The knot consists of an eight residue ring formed by the backbone of residues 57-61 and 102-104 and intramolecular disulfide bridges Cys57-Cys102 and Cys61-Cys104, and a third bridge, Cys26-Cys68, that passes perpendicularly through the ring. Each VEGF-E monomer contains an amino terminal alpha helix and three solvent accessible loop regions, L1, L2, and L3 <scene name='41/411433/Vegf-e_l1_l3/2'>L1 and L3 </scene>.

	are able to form a complex hydrogen bond network as well as extensive hydrophobic contacts with VEGFR making these loops ideal receptor specificity determinants. Residues: P34, S36, T43, P50, R46, D63, E64, and E67 make up the <scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_binding_site/1'>VEGF-E binding pocket </scene>and are critical for binding to VEGFR-2 as determined by alanine mutagenesis.<ref> PMID:16672228</ref> Further, the salt bridge between <scene name='41/411433/Vegf-e_salt_bridge/4'>R46 and E64 </scene> is believed to be the source of VEGF-E’s VEGFR-2 specificity by preventing binding to VEGFR-1. <ref>PMID:15272021</ref>		are able to form a complex hydrogen bond network as well as extensive hydrophobic contacts with VEGFR making these loops ideal receptor specificity determinants. Residues: P34, S36, T43, P50, R46, D63, E64, and E67 make up the <scene name='Vascular_Endothelial_Growth_Factor/Vegf-e_binding_site/1'>VEGF-E binding pocket </scene>and are critical for binding to VEGFR-2 as determined by alanine mutagenesis.<ref> PMID:16672228</ref> Further, the salt bridge between <scene name='41/411433/Vegf-e_salt_bridge/4'>R46 and E64 </scene> is believed to be the source of VEGF-E’s VEGFR-2 specificity by preventing binding to VEGFR-1. <ref>PMID:15272021</ref>