Human SAP AHH SAVE ME MY SAP IS LEAKING

Question 1

What is human sap?

Answer 1

A trace plasma protein that exhibits a small increase in the acute phase. Another carb binding, but this time Ca dependent.

Question 2

What is SAP a constituent of?

Answer 2

Amyloid deposits. Drugs inhibit SAP due to its presence in deposits associated with alzheimers disease.

Question 3

What is spesh about CRP and SAP?

Answer 3

They have 50% sequence homology, 2 antiparallel beta sheets and pentameric aggregation.

Question 4

How do CRP and SAP differ?

Answer 4

Salt bridges in SAP twisted, straight in CRP.

Question 5

unfinished u can do this tomorrow i believe in u son

Answer 5

yes.

Question 6

About human crp ligand binding - how many calcium dependent ligand sites are there on one pentameric face, and what kind of recognition does this suggest?

Answer 6

5 ca dependent ligand binding sites on one pentameric face and this is therefore multivalent recognition.

Question 7

How many calcium ions are in each CRP protomer?

Answer 7

2 calcium ions in each CRP protomer.

Question 8

What is PC (phosphocholine) binding defined by?

Answer 8

• phosphate coordination to Ca ions, Glu81 interacting with the positively charged amine and Phe66 defines hydrophobic pocket.

Question 9

What does PC binding do to the protomer conformation of HCRP?

Answer 9

Does not alter the protomer conformation and does NOT affect C1q binding.

Question 10

What is the substitution for Glu81 and Phe66 (HCRP) in HSAP?

Answer 10

Lys and Tyr

Question 11

What is required for C1q binding?

Answer 11

Conjugated PC

Question 12

What are the HCRP effector functions?

Answer 12

the location of the ligand binding site on one face suggests ‘clamping’ of phospholipid to damaged/foreign cells and effector FUNCTIONS on the other face.

Question 13

What is the structure for the CRP effector face?

Answer 13

A deep extended cleft not present in human SAP - perhaps importand for C1q/receptor binding?

Question 14

Defind the C1q site for HCRP

Answer 14

HCRP pentamer arranged w/a calcium dependent ligand one one face, effector site (C1q, receptors) on other face

Question 15

What is the C1q’s interaction with CRP?

Answer 15

align the predominantly basic head with negatively charged pore of CRP

Question 16

ABOUT DRUG TARGETING: Which two ailments are being chatted about in regards to drug targeting and SAP/HCRP?

Answer 16

amyloidosis and cardiovascular disease

Question 17

Go on about amyloidosis drug targeting.

Answer 17

Targeting human SAP for treatment of amyloidosis because SAP binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. Highly resistant to proteolysis, binding of SAP to amyloid fibrils protects them from degradation. Drug developed - CPHPC, whose carbs bind into the Ca dependent binding pocket. it X links and dimerizes SAP leading to clearance by liver, marked reductions in circulating SAP.

Question 18

Go on about CVS drug targeting

Answer 18

Well, inflammation exacerbated tissue injury in heart attacks and strokes. CRP binds to ligands exposed in damaged tissue and activates complement, leading to an increase in size of damaged area. Inhibitors developed based on crystal structures of ligand bound CRP/SAP and also on the SAP inhibitor.

Question 19

PENTRAXIN EVOLUTION?

Answer 19

EVERY ANIMAL SPECIES OH EM GEE. 200-220 aa, all seq/struc homologous, common ancestor? conserved tertiary fold!! wowza.